\ 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
1051Mental Healthcare for medical staff and affiliated healthcare workers during the COVID-19 pandemic  

The COVID-19 pandemic is an unprecedented challenge for society. Supporting the mental health of medical staff and affiliated healthcare workers (staff) is a critical part of the public health response. This paper details the effects on staff and addresses some of the organisational, team and individual considerations for supporting staff (pragmatically) during this pandemic. Leaders at all levels of health care organisations will find this a valuable resource.

Eur Heart J Acute Cardiovasc C2020       LitCov and CORD-19
1052COVID-19 pandemic and mitigation strategies: implications for maternal and child health and nutrition  

Coronavirus disease 2019 (COVID-19) continues to ravage health and economic metrics globally, including progress in maternal and child nutrition. Although there has been focus on rising rates of childhood wasting in the short term, maternal and child undernutrition rates are also likely to increase as a consequence of COVID-19 and its impacts on poverty, coverage of essential interventions, and access to appropriate nutritious foods. Key sectors at particular risk of collapse or reduced efficiency in the wake of COVID-19 include food systems, incomes, and social protection, health care services for women and children, and services and access to clean water and sanitation. This review highlights key areas of concern for maternal and child nutrition during and in the aftermath of COVID-19 while providing strategic guidance for countries in their efforts to reduce maternal and child undernutrition. Rooted in learnings from the exemplars in Global Health's Stunting Reduction Exemplars project, we provide a set of recommendations that span investments in sectors that have sustained direct and indirect impact on nutrition. These include interventions to strengthen the food-supply chain and reducing food insecurity to assist those at immediate risk of food shortages. Other strategies could include targeted social safety net programs, payment deferrals, or tax breaks as well as suitable cash-support programs for the most vulnerable. Targeting the most marginalized households in rural populations and urban slums could be achieved through deploying community health workers and supporting women and community members. Community-led sanitation programs could be key to ensuring healthy household environments and reducing undernutrition. Additionally, several COVID-19 response measures such as contact tracing and self-isolation could also be exploited for nutrition protection. Global health and improvements in undernutrition will require governments, donors, and development partners to restrategize and reprioritize investments for the COVID-19 era, and will necessitate data-driven decision making, political will and commitment, and international unity.

Am J Clin Nutr2020       LitCov and CORD-19
1053Coronavirus as a possible cause of severe acute respiratory syndrome  

BACKGROUND: An outbreak of severe acute respiratory syndrome (SARS) has been reported in Hong Kong. We investigated the viral cause and clinical presentation among 50 patients. METHODS: We analysed case notes and microbiological findings for 50 patients with SARS, representing more than five separate epidemiologically linked transmission clusters. We defined the clinical presentation and risk factors associated with severe disease and investigated the causal agents by chest radiography and laboratory testing of nasopharyngeal aspirates and sera samples. We compared the laboratory findings with those submitted for microbiological investigation of other diseases from patients whose identity was masked. FINDINGS: Patients' age ranged from 23 to 74 years. Fever, chills, myalgia, and cough were the most frequent complaints. When compared with chest radiographic changes, respiratory symptoms and auscultatory findings were disproportionally mild. Patients who were household contacts of other infected people and had older age, lymphopenia, and liver dysfunction were associated with severe disease. A virus belonging to the family Coronaviridae was isolated from two patients. By use of serological and reverse-transcriptase PCR specific for this virus, 45 of 50 patients with SARS, but no controls, had evidence of infection with this virus. INTERPRETATION: A coronavirus was isolated from patients with SARS that might be the primary agent associated with this disease. Serological and molecular tests specific for the virus permitted a definitive laboratory diagnosis to be made and allowed further investigation to define whether other cofactors play a part in disease progression.

Lancet2003       CORD-19
1054Top Concerns of Tweeters During the COVID-19 Pandemic: Infoveillance Study  

BACKGROUND: The recent coronavirus disease (COVID-19) pandemic is taking a toll on the world’s health care infrastructure as well as the social, economic, and psychological well-being of humanity. Individuals, organizations, and governments are using social media to communicate with each other on a number of issues relating to the COVID-19 pandemic. Not much is known about the topics being shared on social media platforms relating to COVID-19. Analyzing such information can help policy makers and health care organizations assess the needs of their stakeholders and address them appropriately. OBJECTIVE: This study aims to identify the main topics posted by Twitter users related to the COVID-19 pandemic. METHODS: Leveraging a set of tools (Twitter’s search application programming interface (API), Tweepy Python library, and PostgreSQL database) and using a set of predefined search terms (“corona,” “2019-nCov,” and “COVID-19”), we extracted the text and metadata (number of likes and retweets, and user profile information including the number of followers) of public English language tweets from February 2, 2020, to March 15, 2020. We analyzed the collected tweets using word frequencies of single (unigrams) and double words (bigrams). We leveraged latent Dirichlet allocation for topic modeling to identify topics discussed in the tweets. We also performed sentiment analysis and extracted the mean number of retweets, likes, and followers for each topic and calculated the interaction rate per topic. RESULTS: Out of approximately 2.8 million tweets included, 167,073 unique tweets from 160,829 unique users met the inclusion criteria. Our analysis identified 12 topics, which were grouped into four main themes: origin of the virus; its sources; its impact on people, countries, and the economy; and ways of mitigating the risk of infection. The mean sentiment was positive for 10 topics and negative for 2 topics (deaths caused by COVID-19 and increased racism). The mean for tweet topics of account followers ranged from 2722 (increased racism) to 13,413 (economic losses). The highest mean of likes for the tweets was 15.4 (economic loss), while the lowest was 3.94 (travel bans and warnings). CONCLUSIONS: Public health crisis response activities on the ground and online are becoming increasingly simultaneous and intertwined. Social media provides an opportunity to directly communicate health information to the public. Health systems should work on building national and international disease detection and surveillance systems through monitoring social media. There is also a need for a more proactive and agile public health presence on social media to combat the spread of fake news.

J Med Internet Res2020       LitCov and CORD-19
1055Unusual purchasing behavior during the early stages of the COVID-19 pandemic: The stimulus-organism-response approach  

Abstract During the COVID-19 pandemic, unusual consumer behavior, such as hoarding toilet paper, was reported globally. We investigated this behavior when fears of consumer market disruptions started circulating, to capture human behavior in this unique situation. Based on the stimulus-organism-response (S-O-R) framework, we propose a structural model connecting exposure to online information sources (environmental stimuli) to two behavioral responses: unusual purchases and voluntary self-isolation. To test the proposed model, we collected data from 211 Finnish respondents via an online survey, and carried out analysis using PLS-SEM. We found a strong link between self-intention to self-isolate and intention to make unusual purchases, providing empirical evidence that the reported consumer behavior was directly linked to anticipated time spent in self-isolation. The results further revealed exposure to online information sources led to increased information overload and cyberchondria. Information overload was also a strong predictor of cyberchondria. Perceived severity of the situation and cyberchondria had significant impacts on people's intention to make unusual purchases and voluntarily self-isolate. Future research is needed to confirm the long-term effects of the pandemic on consumer and retail services.

N/A2020       CORD-19
1056Proteomic and Metabolomic Characterization of COVID-19 Patient Sera  

Early detection and effective treatment of severe COVID-19 patients remain major challenges. Here, we performed proteomic and metabolomic profiling of sera from 46 COVID-19 and 53 control individuals. We then trained a machine learning model using proteomic and metabolomic measurements from a training cohort of 18 non-severe and 13 severe patients. The model was validated using 10 independent patients, 7 of which were correctly classified. Targeted proteomics and metabolomics assays were employed to further validate this molecular classifier in a second test cohort of 19 COVID-19 patients, leading to 16 correct assignments. We identified molecular changes in the sera of COVID-19 patients compared to other groups implicating dysregulation of macrophage, platelet degranulation, complement system pathways, and massive metabolic suppression. This study revealed characteristic protein and metabolite changes in the sera of severe COVID-19 patients, which might be used in selection of potential blood biomarkers for severity evaluation.

Cell2020       LitCov and CORD-19
1057COVID-19-Related Mental Health Effects in the Workplace: A Narrative Review  

The Coronavirus Disease 2019 (COVID-19) pandemic has deeply altered social and working environments in several ways. Social distancing policies, mandatory lockdowns, isolation periods, and anxiety of getting sick, along with the suspension of productive activity, loss of income, and fear of the future, jointly influence the mental health of citizens and workers. Workplace aspects can play a crucial role on moderating or worsening mental health of people facing this pandemic scenario. The purpose of this literature review is to deepen the psychological aspects linked to workplace factors, following the epidemic rise of COVID-19, in order to address upcoming psychological critical issues in the workplaces. We performed a literature search using Google Scholar, PubMed, and Scopus, selecting papers focusing on workers’ psychological problems that can be related to the workplace during the pandemic. Thirty-five articles were included. Mental issues related to the health emergency, such as anxiety, depression, post-traumatic stress disorder (PTSD), and sleep disorders are more likely to affect healthcare workers, especially those on the frontline, migrant workers, and workers in contact with the public. Job insecurity, long periods of isolation, and uncertainty of the future worsen the psychological condition, especially in younger people and in those with a higher educational background. Multiple organizational and work-related interventions can mitigate this scenario, such as the improvement of workplace infrastructures, the adoption of correct and shared anti-contagion measures, including regular personal protective equipment (PPE) supply, and the implementation of resilience training programs. This review sets the basis for a better understanding of the psychological conditions of workers during the pandemic, integrating individual and social perspectives, and providing insight into possible individual, social, and occupational approaches to this “psychological pandemic”.

Int J Environ Res Public Healt2020       LitCov and CORD-19
1058Risk factors for severe and critically ill COVID-19 patients: A review  

N/A

Allergy2021       LitCov and CORD-19
1059Hepatocellular carcinoma  

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Nat Rev Dis Primers2021       CORD-19
1060Global, regional and national estimates of the population at increased risk of severe COVID-19 due to underlying health conditions in 2020: a modelling study  

BACKGROUND: The risk of severe COVID-19 if an individual becomes infected is known to be higher in older individuals and those with underlying health conditions. Understanding the number of individuals at increased risk of severe COVID-19 and how this varies between countries should inform the design of possible strategies to shield or vaccinate those at highest risk. METHODS: We estimated the number of individuals at increased risk of severe disease (defined as those with at least one condition listed as “at increased risk of severe COVID-19” in current guidelines) by age (5-year age groups), sex, and country for 188 countries using prevalence data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 and UN population estimates for 2020. The list of underlying conditions relevant to COVID-19 was determined by mapping the conditions listed in GBD 2017 to those listed in guidelines published by WHO and public health agencies in the UK and the USA. We analysed data from two large multimorbidity studies to determine appropriate adjustment factors for clustering and multimorbidity. To help interpretation of the degree of risk among those at increased risk, we also estimated the number of individuals at high risk (defined as those that would require hospital admission if infected) using age-specific infection–hospitalisation ratios for COVID-19 estimated for mainland China and making adjustments to reflect country-specific differences in the prevalence of underlying conditions and frailty. We assumed males were twice at likely as females to be at high risk. We also calculated the number of individuals without an underlying condition that could be considered at increased risk because of their age, using minimum ages from 50 to 70 years. We generated uncertainty intervals (UIs) for our estimates by running low and high scenarios using the lower and upper 95% confidence limits for country population size, disease prevalences, multimorbidity fractions, and infection–hospitalisation ratios, and plausible low and high estimates for the degree of clustering, informed by multimorbidity studies. FINDINGS: We estimated that 1·7 billion (UI 1·0–2·4) people, comprising 22% (UI 15–28) of the global population, have at least one underlying condition that puts them at increased risk of severe COVID-19 if infected (ranging from <5% of those younger than 20 years to >66% of those aged 70 years or older). We estimated that 349 million (186–787) people (4% [3–9] of the global population) are at high risk of severe COVID-19 and would require hospital admission if infected (ranging from <1% of those younger than 20 years to approximately 20% of those aged 70 years or older). We estimated 6% (3–12) of males to be at high risk compared with 3% (2–7) of females. The share of the population at increased risk was highest in countries with older populations, African countries with high HIV/AIDS prevalence, and small island nations with high diabetes prevalence. Estimates of the number of individuals at increased risk were most sensitive to the prevalence of chronic kidney disease, diabetes, cardiovascular disease, and chronic respiratory disease. INTERPRETATION: About one in five individuals worldwide could be at increased risk of severe COVID-19, should they become infected, due to underlying health conditions, but this risk varies considerably by age. Our estimates are uncertain, and focus on underlying conditions rather than other risk factors such as ethnicity, socioeconomic deprivation, and obesity, but provide a starting point for considering the number of individuals that might need to be shielded or vaccinated as the global pandemic unfolds. FUNDING: UK Department for International Development, Wellcome Trust, Health Data Research UK, Medical Research Council, and National Institute for Health Research.

Lancet Glob Health2020       LitCov and CORD-19
1061Assessment of the Evolution of Cancer Treatment Therapies  

Cancer therapy has been characterized throughout history by ups and downs, not only due to the ineffectiveness of treatments and side effects, but also by hope and the reality of complete remission and cure in many cases. Within the therapeutic arsenal, alongside surgery in the case of solid tumors, are the antitumor drugs and radiation that have been the treatment of choice in some instances. In recent years, immunotherapy has become an important therapeutic alternative, and is now the first choice in many cases. Nanotechnology has recently arrived on the scene, offering nanostructures as new therapeutic alternatives for controlled drug delivery, for combining imaging and treatment, applying hyperthermia, and providing directed target therapy, among others. These therapies can be applied either alone or in combination with other components (antibodies, peptides, folic acid, etc.). In addition, gene therapy is also offering promising new methods for treatment. Here, we present a review of the evolution of cancer treatments, starting with chemotherapy, surgery, radiation and immunotherapy, and moving on to the most promising cutting-edge therapies (gene therapy and nanomedicine). We offer an historical point of view that covers the arrival of these therapies to clinical practice and the market, and the promises and challenges they present.

Cancers (Basel)2011       CORD-19
1062The novel coronavirus (COVID-2019) outbreak: Amplification of public health consequences by media exposure  

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Health Psychol2020       LitCov and CORD-19
1063Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19: The CoDEX Randomized Clinical Trial  

N/A

JAMA2020       LitCov and CORD-19
1064COVID-19 in elderly patients: Characteristics and prognostic factors based on 4-week follow-up  

OBJECTIVE: To investigate the characteristics and prognostic factors in the elderly patients with COVID-19. METHODS: Consecutive cases over 60 years old with COVID-19 in Renmin Hospital of Wuhan University from Jan 1 to Feb 6, 2020 were included. The primary outcomes were death and survival till March 5. Data of demographics, clinical features, comorbidities, laboratory tests and complications were collected and compared for different outcomes. Cox regression was performed for prognostic factors. RESULTS: 339 patients with COVID-19 (aged 71±8 years,173 females (51%)) were enrolled, including 80 (23.6%) critical, 159 severe (46.9%) and 100 moderate (29.5%) cases. Common comorbidities were hypertension (40.8%), diabetes (16.0%) and cardiovascular disease (15.7%). Common symptoms included fever (92.0%), cough (53.0%), dyspnea (40.8%) and fatigue (39.9%). Lymphocytopenia was a common laboratory finding (63.2%). Common complications included bacterial infection (42.8%), liver enzyme abnormalities (28.7%) and acute respiratory distress syndrome (21.0%). Till Mar 5, 2020, 91 cases were discharged (26.8%), 183 cases stayed in hospital (54.0%) and 65 cases (19.2%) were dead. Shorter length of stay was found for the dead compared with the survivors (5 (3–8) vs. 28 (26–29), P < 0.001). Symptoms of dyspnea (HR 2.35, P = 0.001), comorbidities including cardiovascular disease (HR 1.86, P = 0.031) and chronic obstructive pulmonary disease (HR 2.24, P = 0.023), and acute respiratory distress syndrome (HR 29.33, P < 0.001) were strong predictors of death. And a high level of lymphocytes was predictive of better outcome (HR 0.10, P < 0.001). CONCLUSIONS: High proportion of severe to critical cases and high fatality rate were observed in the elderly COVID-19 patients. Rapid disease progress was noted in the dead with a median survival time of 5 days after admission. Dyspnea, lymphocytopenia, comorbidities including cardiovascular disease and chronic obstructive pulmonary disease, and acute respiratory distress syndrome were predictive of poor outcome. Close monitoring and timely treatment should be performed for the elderly patients at high risk.

J Infect2020       LitCov and CORD-19
1065Severe Acute Respiratory Syndrome (SARS)  

Severe acute respiratory syndrome (SARS) is a new human disease caused by an animal coronavirus that adapted to efficient human-to-human transmission. The disease first emerged in November 2002 in Guangdong Province, China and spread globally within months. The SARS coronavirus (SARS CoV) affects multiple organ systems with severe viral pneumonia as its main clinical manifestation but with diarrhea, lymphopenia, and mild liver dysfunction being common extra-pulmonary manifestations. Increasing age and the presence of underlying respiratory diseases worsens the prognosis. Unlike other respiratory viral infections, transmission of SARS was less frequent in the first 5 days of illness and correlated with low viral load in the upper respiratory tract at this stage of the illness. This fortuitous feature of the disease allowed the public health measures of case detection and patient isolation to interrupt virus transmission in the community and abort the SARS outbreak. Bats are a reservoir of a virus closely related to SARS CoV and this may be the likely precursor from which the human-adapted SARS CoV emerged. Small mammals such as ‘civet-cats’ (Paguma larvata) within live animal markets in southern China serve as amplifiers of infection and these markets were the likely interface where zoonotic transmission occurred. The viral spike protein is necessary and sufficient for inducing protective antibody responses and has been a key target in the development of candidate vaccines.

Encyclopedia of Virology2008       CORD-19
1066The Impact of Social Media on Panic During the COVID-19 Pandemic in Iraqi Kurdistan: Online Questionnaire Study  

BACKGROUND: In the first few months of 2020, information and news reports about the coronavirus disease (COVID-19) were rapidly published and shared on social media and social networking sites. While the field of infodemiology has studied information patterns on the Web and in social media for at least 18 years, the COVID-19 pandemic has been referred to as the first social media infodemic. However, there is limited evidence about whether and how the social media infodemic has spread panic and affected the mental health of social media users. OBJECTIVE: The aim of this study is to determine how social media affects self-reported mental health and the spread of panic about COVID-19 in the Kurdistan Region of Iraq. METHODS: To carry out this study, an online questionnaire was prepared and conducted in Iraqi Kurdistan, and a total of 516 social media users were sampled. This study deployed a content analysis method for data analysis. Correspondingly, data were analyzed using SPSS software. RESULTS: Participants reported that social media has a significant impact on spreading fear and panic related to the COVID-19 outbreak in Iraqi Kurdistan, with a potential negative influence on people’s mental health and psychological well-being. Facebook was the most used social media network for spreading panic about the COVID-19 outbreak in Iraq. We found a significant positive statistical correlation between self-reported social media use and the spread of panic related to COVID-19 (R=.8701). Our results showed that the majority of youths aged 18-35 years are facing psychological anxiety. CONCLUSIONS: During lockdown, people are using social media platforms to gain information about COVID-19. The nature of the impact of social media panic among people varies depending on an individual's gender, age, and level of education. Social media has played a key role in spreading anxiety about the COVID-19 outbreak in Iraqi Kurdistan.

J Med Internet Res2020       LitCov and CORD-19
1067Severe acute respiratory syndrome-SARS  

N/A

Ugeskr Laeger2003       CORD-19
1068Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination  

BACKGROUND: Several cases of unusual thrombotic events and thrombocytopenia have developed after vaccination with the recombinant adenoviral vector encoding the spike protein antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (ChAdOx1 nCov-19, AstraZeneca). More data were needed on the pathogenesis of this unusual clotting disorder. METHODS: We assessed the clinical and laboratory features of 11 patients in Germany and Austria in whom thrombosis or thrombocytopenia had developed after vaccination with ChAdOx1 nCov-19. We used a standard enzyme-linked immunosorbent assay to detect platelet factor 4 (PF4)–heparin antibodies and a modified (PF4-enhanced) platelet-activation test to detect platelet-activating antibodies under various reaction conditions. Included in this testing were samples from patients who had blood samples referred for investigation of vaccine-associated thrombotic events, with 28 testing positive on a screening PF4–heparin immunoassay. RESULTS: Of the 11 original patients, 9 were women, with a median age of 36 years (range, 22 to 49). Beginning 5 to 16 days after vaccination, the patients presented with one or more thrombotic events, with the exception of 1 patient, who presented with fatal intracranial hemorrhage. Of the patients with one or more thrombotic events, 9 had cerebral venous thrombosis, 3 had splanchnic-vein thrombosis, 3 had pulmonary embolism, and 4 had other thromboses; of these patients, 6 died. Five patients had disseminated intravascular coagulation. None of the patients had received heparin before symptom onset. All 28 patients who tested positive for antibodies against PF4–heparin tested positive on the platelet-activation assay in the presence of PF4 independent of heparin. Platelet activation was inhibited by high levels of heparin, Fc receptor–blocking monoclonal antibody, and immune globulin (10 mg per milliliter). Additional studies with PF4 or PF4–heparin affinity purified antibodies in 2 patients confirmed PF4-dependent platelet activation. CONCLUSIONS: Vaccination with ChAdOx1 nCov-19 can result in the rare development of immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against PF4, which clinically mimics autoimmune heparin-induced thrombocytopenia. (Funded by the German Research Foundation.)

N Engl J Med2021       LitCov and CORD-19
1069Clinical Features of 85 Fatal Cases of COVID-19 from Wuhan. A Retrospective Observational Study  

Rationale: The global death toll from coronavirus disease (COVID-19) virus as of May 12, 2020, exceeds 286,000. The risk factors for death were attributed to advanced age and comorbidities but have not been accurately defined. Objectives: To report the clinical features of 85 fatal cases of COVID-19 in two hospitals in Wuhan. Methods: Medical records were collected of 85 fatal cases of COVID-19 between January 9, 2020, and February 15, 2020. Information recorded included medical history, exposure history, comorbidities, symptoms, signs, laboratory findings, computed tomographic scans, and clinical management. Measurements and Main Results: The median age of the patients was 65.8 years, and 72.9% were male. Common symptoms were fever (78 [91.8%]), shortness of breath (50 [58.8%]), fatigue (50 [58.8%]), and dyspnea (60 [70.6%]). Hypertension, diabetes, and coronary heart disease were the most common comorbidities. Notably, 81.2% of patients had very low eosinophil counts on admission. Complications included respiratory failure (80 [94.1%]), shock (69 [81.2%]), acute respiratory distress syndrome (63 [74.1%]), and arrhythmia (51 [60%]), among others. Most patients received antibiotic (77 [90.6%]), antiviral (78 [91.8%]), and glucocorticoid (65 [76.5%]) treatments. A total of 38 (44.7%) and 33 (38.8%) patients received intravenous immunoglobulin and IFN-α2b, respectively. Conclusions: In this depictive study of 85 fatal cases of COVID-19, most cases were males aged over 50 years with noncommunicable chronic diseases. The majority of the patients died of multiple organ failure. Early onset of shortness of breath may be used as an observational symptom for COVID-19 exacerbations. Eosinophilopenia may indicate a poor prognosis. A combination of antimicrobial drugs did not offer considerable benefit to the outcome of this group of patients.

Am J Respir Crit Care Med2020       LitCov and CORD-19
1070Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: a prospective cohort study  

To identify factors associated with the death for patients with COVID-19 pneumonia caused by a novel coronavirus SARS-CoV-2. All clinical and laboratory parameters were collected prospectively from a cohort of patients with COVID-19 pneumonia who were hospitalised to Wuhan Pulmonary Hospital, Wuhan City, Hubei Province, China, between December 25, 2019 and February 7, 2020. Univariate and multivariate logistic regression was performed to investigate the relationship between each variable and the risk for death of COVID-19 pneumonia patients. A total of 179 patients with COVID-19 pneumonia (97 male and 82 female) were included in the present prospective study, of whom 21 died. Univariate and multivariate logistic regression analysis revealed that age ≥65 years (odd ratio, 3.765; 95% confidence interval, 1.146‒17.394; p=0.023), preexisting concurrent cardiovascular or cerebrovascular diseases (2.464; 0.755‒8.044; p=0.007), CD3(+)CD8(+) T cells ≤75 cell·μL(−1) (3.982; 1.132‒14.006; p<0.001), and cardiac troponin I≥0.05 ng·mL(−1) (4.077; 1.166‒14.253; p<0.001) were associated with an increase in risk of mortality of COVID-19 pneumonia. In the sex‒, age‒, and comorbid illness-matched case study, CD3(+)CD8(+) T cells ≤75 cell·μL(−1) and cardiac troponin I≥0.05 ng·mL(−1) remained to be the predictors for high mortality of COVID-19 pneumonia. We identified four risk factors, age ≥65 years, preexisting concurrent cardiovascular or cerebrovascular diseases, CD3(+)CD8(+) T cells ≤75 cell·μL(−1), and cardiac troponin I≥0.05 ng·mL(−1), especially the latter two factors, were predictors for mortality of COVID-19 pneumonia patients.

Eur Respir J2020       LitCov and CORD-19
1071Impact of COVID-19 on the travel and tourism industry  

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Technol Forecast Soc Change2021       LitCov
1072Head and neck squamous cell carcinoma  

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Nat Rev Dis Primers2020       CORD-19
1073Overlapping and discrete aspects of the pathology and pathogenesis of the emerging human pathogenic coronaviruses SARS-CoV, MERS-CoV and 2019-nCoV  

First reported from Wuhan, The People's Republic of China, on 31 December 2019, the ongoing outbreak of a novel coronavirus (2019‐nCoV) causes great global concerns. Based on the advice of the International Health Regulations Emergency Committee and the fact that to date 24 other countries also reported cases, the WHO Director‐General declared that the outbreak of 2019‐nCoV constitutes a Public Health Emergency of International Concern on 30 January 2020. Together with the other two highly pathogenic coronaviruses, the severe acute respiratory syndrome coronavirus (SARS‐CoV) and Middle East respiratory syndrome coronavirus (MERS‐CoV), 2019‐nCov and other yet to be identified coronaviruses pose a global threat to public health. In this mini‐review, we provide a brief introduction to the pathology and pathogenesis of SARS‐CoV and MERS‐CoV and extrapolate this knowledge to the newly identified 2019‐nCoV.

J Med Virol2020       LitCov and CORD-19
1074Long covid-mechanisms, risk factors and management  

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BMJ2021       LitCov and CORD-19
1075COVID-19 Pandemic and Lockdown Measures Impact on Mental Health Among the General Population in Italy  

BACKGROUND: The psychological impact of the COronaVIrus Disease 2019 (COVID-19) outbreak and lockdown measures on the Italian population are unknown. The current study assesses rates of mental health outcomes in the Italian general population three to 4 weeks into lockdown measures and explores the impact of COVID-19 related potential risk factors. METHODS: A web-based survey spread throughout the internet between March 27(th) and April 6(th) 2020. Eighteen thousand one hundred forty-seven individuals completed the questionnaire, 79.6% women. Selected outcomes were post-traumatic stress symptoms (PTSS), depression, anxiety, insomnia, perceived stress, and adjustment disorder symptoms (ADS). Seemingly unrelated logistic regression analysis was performed to identify COVID-19 related risk factors. RESULTS: Endorsement rates for PTSS were 6,604 (37%), 3,084 (17.3%) for depression, 3,700 (20.8%) for anxiety, 1,301 (7.3%) for insomnia, 3,895 (21.8%) for high perceived stress and 4,092 (22.9%) for adjustment disorder. Being woman and younger age were associated with all of the selected outcomes. Quarantine was associated with PTSS, anxiety and ADS. Any recent COVID-related stressful life event was associated with all the selected outcomes. Discontinued working activity due to the COVID-19 was associated with all the selected outcomes, except for ADS; working more than usual was associated with PTSS, Perceived stress and ADS. Having a loved one deceased by COVID-19 was associated with PTSS, depression, perceived stress, and insomnia. CONCLUSION: We found high rates of negative mental health outcomes in the Italian general population 3 weeks into the COVID-19 lockdown measures and different COVID-19 related risk factors. These findings warrant further monitoring on the Italian population’s mental health.

Front Psychiatry2020       LitCov and CORD-19
1076Physical activity, diet and other behavioural interventions for improving cognition and school achievement in children and adolescents with obesity or overweight  

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Cochrane Database Syst Rev2018       CORD-19
1077Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State  

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JAMA2020       LitCov and CORD-19
1078Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues  

BACKGROUND: Since its discovery in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 2 180 000 people worldwide and has caused more than 150 000 deaths as of April 16, 2020. SARS-CoV-2, which is the virus causing coronavirus disease 2019 (COVID-19), uses the angiotensin-converting enzyme 2 (ACE2) as a cell receptor to invade human cells. Thus, ACE2 is the key to understanding the mechanism of SARS-CoV-2 infection. This study is to investigate the ACE2 expression in various human tissues in order to provide insights into the mechanism of SARS-CoV-2 infection. METHODS: We compared ACE2 expression levels across 31 normal human tissues between males and females and between younger (ages ≤ 49 years) and older (ages > 49 years) persons using two-sided Student’s t test. We also investigated the correlations between ACE2 expression and immune signatures in various tissues using Pearson’s correlation test. RESULTS: ACE2 expression levels were the highest in the small intestine, testis, kidneys, heart, thyroid, and adipose tissue, and were the lowest in the blood, spleen, bone marrow, brain, blood vessels, and muscle. ACE2 showed medium expression levels in the lungs, colon, liver, bladder, and adrenal gland. ACE2 was not differentially expressed between males and females or between younger and older persons in any tissue. In the skin, digestive system, brain, and blood vessels, ACE2 expression levels were positively associated with immune signatures in both males and females. In the thyroid and lungs, ACE2 expression levels were positively and negatively associated with immune signatures in males and females, respectively, and in the lungs they had a positive and a negative correlation in the older and younger groups, respectively. CONCLUSIONS: Our data indicate that SARS-CoV-2 may infect other tissues aside from the lungs and infect persons with different sexes, ages, and races equally. The different host immune responses to SARS-CoV-2 infection may partially explain why males and females, young and old persons infected with this virus have markedly distinct disease severity. This study provides new insights into the role of ACE2 in the SARS-CoV-2 pandemic.

Infect Dis Poverty2020       LitCov and CORD-19
1079Composition and divergence of coronavirus spike proteins and host ACE2 receptors predict potential intermediate hosts of SARS-CoV-2  

From the beginning of 2002 and 2012, severe respiratory syndrome coronavirus (SARS‐CoV) and Middle East respiratory syndrome coronavirus (MERS‐CoV) crossed the species barriers to infect humans, causing thousands of infections and hundreds of deaths, respectively. Currently, a novel coronavirus (SARS‐CoV‐2), which has become the cause of the outbreak of Coronavirus Disease 2019 (COVID‐19), was discovered. Until 18 February 2020, there were 72 533 confirmed COVID‐19 cases (including 10 644 severe cases) and 1872 deaths in China. SARS‐CoV‐2 is spreading among the public and causing substantial burden due to its human‐to‐human transmission. However, the intermediate host of SARS‐CoV‐2 is still unclear. Finding the possible intermediate host of SARS‐CoV‐2 is imperative to prevent further spread of the epidemic. In this study, we used systematic comparison and analysis to predict the interaction between the receptor‐binding domain (RBD) of coronavirus spike protein and the host receptor, angiotensin‐converting enzyme 2 (ACE2). The interaction between the key amino acids of S protein RBD and ACE2 indicated that, other than pangolins and snakes, as previously suggested, turtles (Chrysemys picta bellii, Chelonia mydas, and Pelodiscus sinensis) may act as the potential intermediate hosts transmitting SARS‐CoV‐2 to humans.

J Med Virol2020       LitCov and CORD-19
1080Coronavirus Disease 19: Implications for Clinical Dental Care  

The recent spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated coronavirus disease has gripped the entire international community and caused widespread public health concerns. Despite global efforts to contain the disease spread, the outbreak is still on a rise because of the community spread pattern of this infection. This is a zoonotic infection, similar to other coronavirus infections, that is believed to have originated in bats and pangolins and later transmitted to humans. Once in the human body, this coronavirus (SARS-CoV-2) is abundantly present in nasopharyngeal and salivary secretions of affected patients, and its spread is predominantly thought to be respiratory droplet/contact in nature. Dental professionals, including endodontists, may encounter patients with suspected or confirmed SARS-CoV-2 infection and will have to act diligently not only to provide care but at the same time prevent nosocomial spread of infection. Thus, the aim of this article is to provide a brief overview of the epidemiology, symptoms, and routes of transmission of this novel infection. In addition, specific recommendations for dental practice are suggested for patient screening, infection control strategies, and patient management protocol.

J Endod2020       LitCov and CORD-19
1081The InterPro protein families and domains database: 20 years on  

The InterPro database (https://www.ebi.ac.uk/interpro/) provides an integrative classification of protein sequences into families, and identifies functionally important domains and conserved sites. InterProScan is the underlying software that allows protein and nucleic acid sequences to be searched against InterPro's signatures. Signatures are predictive models which describe protein families, domains or sites, and are provided by multiple databases. InterPro combines signatures representing equivalent families, domains or sites, and provides additional information such as descriptions, literature references and Gene Ontology (GO) terms, to produce a comprehensive resource for protein classification. Founded in 1999, InterPro has become one of the most widely used resources for protein family annotation. Here, we report the status of InterPro (version 81.0) in its 20th year of operation, and its associated software, including updates to database content, the release of a new website and REST API, and performance improvements in InterProScan.

Nucleic Acids Res2020       LitCov and CORD-19
1082A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology  

The ongoing pandemic spread of a novel human coronavirus, SARS-COV-2, associated with severe pneumonia disease (COVID-19), has resulted in the generation of tens of thousands of virus genome sequences. The rate of genome generation is unprecedented, yet there is currently no coherent nor accepted scheme for naming the expanding phylogenetic diversity of SARS-CoV-2. We present a rational and dynamic virus nomenclature that uses a phylogenetic framework to identify those lineages that contribute most to active spread. Our system is made tractable by constraining the number and depth of hierarchical lineage labels and by flagging and de-labelling virus lineages that become unobserved and hence are likely inactive. By focusing on active virus lineages and those spreading to new locations this nomenclature will assist in tracking and understanding the patterns and determinants of the global spread of SARS-CoV-2.

Nat Microbiol2020       LitCov and CORD-19
1083Evolution of antibody immunity to SARS-CoV-2  

N/A

Nature2021       LitCov and CORD-19
1084Learning from the Past: Possible Urgent Prevention and Treatment Options for Severe Acute Respiratory Infections Caused by 2019-nCoV  

With the current trajectory of the 2019‐nCoV outbreak unknown, public health and medicinal measures will both be needed to contain spreading of the virus and to optimize patient outcomes. Although little is known about the virus, an examination of the genome sequence shows strong homology with its better‐studied cousin, SARS‐CoV. The spike protein used for host cell infection shows key nonsynonymous mutations that might hamper the efficacy of previously developed therapeutics but remains a viable target for the development of biologics and macrocyclic peptides. Other key drug targets, including RNA‐dependent RNA polymerase and coronavirus main proteinase (3CLpro), share a strikingly high (>95 %) homology to SARS‐CoV. Herein, we suggest four potential drug candidates (an ACE2‐based peptide, remdesivir, 3CLpro‐1 and a novel vinylsulfone protease inhibitor) that could be used to treat patients suffering with the 2019‐nCoV. We also summarize previous efforts into drugging these targets and hope to help in the development of broad‐spectrum anti‐coronaviral agents for future epidemics.

Chembiochem2020       LitCov and CORD-19
1085Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China  

Although the respiratory and immune systems are the major targets of Coronavirus Disease 2019 (COVID-19), acute kidney injury and proteinuria have also been observed. Currently, detailed pathologic examination of kidney damage in critically ill patients with COVID-19 has been lacking. To help define this we analyzed kidney abnormalities in 26 autopsies of patients with COVID-19 by light microscopy, ultrastructural observation and immunostaining. Patients were on average 69 years (19 male and 7 female) with respiratory failure associated with multiple organ dysfunction syndrome as the cause of death. Nine of the 26 showed clinical signs of kidney injury that included increased serum creatinine and/or new-onset proteinuria. By light microscopy, diffuse proximal tubule injury with the loss of brush border, non-isometric vacuolar degeneration, and even frank necrosis was observed. Occasional hemosiderin granules and pigmented casts were identified. There were prominent erythrocyte aggregates obstructing the lumen of capillaries without platelet or fibrinoid material. Evidence of vasculitis, interstitial inflammation or hemorrhage was absent. Electron microscopic examination showed clusters of coronavirus particles with distinctive spikes in the tubular epithelium and podocytes. Furthermore, the receptor of SARS-CoV-2, ACE2 was found to be upregulated in patients with COVID-19, and immunostaining with SARS-CoV nucleoprotein antibody was positive in tubules. In addition to the direct virulence of SARS-CoV-2, factors contributing to acute kidney injury included systemic hypoxia, abnormal coagulation, and possible drug or hyperventilation-relevant rhabdomyolysis. Thus, our studies provide direct evidence of the invasion of SARSCoV-2 into kidney tissue. These findings will greatly add to the current understanding of SARS-CoV-2 infection.

Kidney Int2020       LitCov and CORD-19
1086Cutaneous manifestations in COVID-19: a first perspective  

N/A

J Eur Acad Dermatol Venereol2020       LitCov and CORD-19
1087Clinical characteristics and outcomes of patients undergoing surgeries during the incubation period of COVID-19 infection  

BACKGROUND: The outbreak of 2019 novel coronavirus disease (COVID-19) in Wuhan, China, has spread rapidly worldwide. In the early stage, we encountered a small but meaningful number of patients who were unintentionally scheduled for elective surgeries during the incubation period of COVID-19. We intended to describe their clinical characteristics and outcomes. METHODS: We retrospectively analyzed the clinical data of 34 patients underwent elective surgeries during the incubation period of COVID-19 at Renmin Hospital, Zhongnan Hospital, Tongji Hospital and Central Hospital in Wuhan, from January 1 to February 5, 2020. FINDINGS: Of the 34 operative patients, the median age was 55 years (IQR, 43–63), and 20 (58·8%) patients were women. All patients developed COVID-19 pneumonia shortly after surgery with abnormal findings on chest computed tomographic scans. Common symptoms included fever (31 [91·2%]), fatigue (25 [73·5%]) and dry cough (18 [52·9%]). 15 (44·1%) patients required admission to intensive care unit (ICU) during disease progression, and 7 patients (20·5%) died after admission to ICU. Compared with non-ICU patients, ICU patients were older, were more likely to have underlying comorbidities, underwent more difficult surgeries, as well as more severe laboratory abnormalities (eg, hyperleukocytemia, lymphopenia). The most common complications in non-survivors included ARDS, shock, arrhythmia and acute cardiac injury. INTERPRETATION: In this retrospective cohort study of 34 operative patients with confirmed COVID-19, 15 (44·1%) patients needed ICU care, and the mortality rate was 20·5%. FUNDING: National Natural Science Foundation of China.

EClinicalMedicine2020       LitCov and CORD-19
1088A Review of the Progress and Challenges of Developing a Vaccine for COVID-19  

A novel coronavirus, which has been designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first detected in December 2019 in Wuhan China and causes the highly infectious disease referred to as COVID-19. COVID-19 has now spread worldwide to become a global pandemic affecting over 24 million people as of August 26th, 2020 and claimed the life of more than 800,000 people worldwide. COVID-19 is asymptomatic for some individuals and for others it can cause symptoms ranging from flu-like to acute respiratory distress syndrome (ARDS), pneumonia and death. Although it is anticipated that an effective vaccine will be available to protect against COVID-19, at present the world is relying on social distancing and hygiene measures and repurposed drugs. There is a worldwide effort to develop an effective vaccine against SARS-CoV-2 and, as of late August 2020, there are 30 vaccines in clinical trials with over 200 in various stages of development. This review will focus on the eight vaccine candidates that entered Phase 1 clinical trials in mid-May, including AstraZeneca/Oxford's AZD1222, Moderna's mRNA-1273 and Sinovac's CoronaVac vaccines, which are currently in advanced stages of vaccine development. In addition to reviewing the different stages of vaccine development, vaccine platforms and vaccine candidates, this review also discusses the biological and immunological basis required of a SARS-CoV-2 vaccine, the importance of a collaborative international effort, the ethical implications of vaccine development, the efficacy needed for an immunogenic vaccine, vaccine coverage, the potential limitations and challenges of vaccine development. Although the demand for a vaccine far surpasses the production capacity, it will be beneficial to have a limited number of vaccines available for the more vulnerable population by the end of 2020 and for the rest of the global population by the end of 2021.

Front Immunol2020       LitCov and CORD-19
1089Global hotspots and correlates of emerging zoonotic diseases  

Zoonoses originating from wildlife represent a significant threat to global health, security and economic growth, and combatting their emergence is a public health priority. However, our understanding of the mechanisms underlying their emergence remains rudimentary. Here we update a global database of emerging infectious disease (EID) events, create a novel measure of reporting effort, and fit boosted regression tree models to analyze the demographic, environmental and biological correlates of their occurrence. After accounting for reporting effort, we show that zoonotic EID risk is elevated in forested tropical regions experiencing land-use changes and where wildlife biodiversity (mammal species richness) is high. We present a new global hotspot map of spatial variation in our zoonotic EID risk index, and partial dependence plots illustrating relationships between events and predictors. Our results may help to improve surveillance and long-term EID monitoring programs, and design field experiments to test underlying mechanisms of zoonotic disease emergence.

Nat Commun2017       CORD-19
1090Insight into 2019 novel coronavirus-An updated interim review and lessons from SARS-CoV and MERS-CoV  

BACKGROUND: The rapid spread of the coronavirus disease 2019 (COVID-19), caused by a zoonotic beta-coronavirus entitled 2019 novel coronavirus (2019-nCoV), has become a global threat. Awareness of the biological features of 2019-nCoV should be updated in time and needs to be comprehensively summarized to help optimize control measures and make therapeutic decisions. METHODS: Based on recently published literatures, official documents and selected up-to-date preprint studies, we reviewed the virology and origin, epidemiology, clinical manifestations, pathology and treatment of 2019-nCoV infection, in comparison with severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV) infection. RESULTS: The genome of 2019-nCoV partially resembled SARS-CoV and MERS-CoV, and indicating a bat origin. The COVID-19 generally had a high reproductive number, a long incubation period, a short serial interval and a low case fatality rate (much higher in patients with comorbidities) than SARS and MERS. Clinical presentation and pathology of COVID-19 greatly resembled SARS and MERS, with less upper respiratory and gastrointestinal symptoms, and more exudative lesions in post-mortems. Potential treatments included remdesivir, chloroquine, tocilizumab, convalescent plasma and vaccine immunization (when possible). CONCLUSION: The initial experience from the current pandemic and lessons from the previous two pandemics can help improve future preparedness plans and combat disease progression.

Int J Infect Dis2020       LitCov and CORD-19
1091A systematic review of antibody mediated immunity to coronaviruses: kinetics, correlates of protection and association with severity  

Many public health responses and modeled scenarios for COVID-19 outbreaks caused by SARS-CoV-2 assume that infection results in an immune response that protects individuals from future infections or illness for some amount of time. The presence or absence of protective immunity due to infection or vaccination (when available) will affect future transmission and illness severity. Here, we review the scientific literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV, MERS-CoV and endemic human coronaviruses (HCoVs). We reviewed 2,452 abstracts and identified 491 manuscripts relevant to 5 areas of focus: 1) antibody kinetics, 2) correlates of protection, 3) immunopathogenesis, 4) antigenic diversity and cross-reactivity, and 5) population seroprevalence. While further studies of SARS-CoV-2 are necessary to determine immune responses, evidence from other coronaviruses can provide clues and guide future research.

Nat Commun2020       LitCov and CORD-19
1092Bacterial coinfection and secondary infection in patients with COVID-19: a living rapid review and meta-analysis  

BACKGROUND: Bacterial co-pathogens are commonly identified in viral respiratory infections and are important causes of morbidity and mortality. The prevalence of bacterial infection in patients infected with SARS-CoV-2 is not well understood. AIMS: To determine the prevalence of bacterial co-infection (at presentation) and secondary infection (after presentation) in patients with COVID-19. SOURCES: We performed a systematic search of MEDLINE, OVID Epub and EMBASE databases for English language literature from 2019 to April 16, 2020. Studies were included if they (a) evaluated patients with confirmed COVID-19 and (b) reported the prevalence of acute bacterial infection. CONTENT: Data were extracted by a single reviewer and cross-checked by a second reviewer. The main outcome was the proportion of COVID-19 patients with an acute bacterial infection. Any bacteria detected from non-respiratory-tract or non-bloodstream sources were excluded. Of 1308 studies screened, 24 were eligible and included in the rapid review representing 3338 patients with COVID-19 evaluated for acute bacterial infection. In the meta-analysis, bacterial co-infection (estimated on presentation) was identified in 3.5% of patients (95%CI 0.4–6.7%) and secondary bacterial infection in 14.3% of patients (95%CI 9.6–18.9%). The overall proportion of COVID-19 patients with bacterial infection was 6.9% (95%CI 4.3–9.5%). Bacterial infection was more common in critically ill patients (8.1%, 95%CI 2.3–13.8%). The majority of patients with COVID-19 received antibiotics (71.9%, 95%CI 56.1 to 87.7%). IMPLICATIONS: Bacterial co-infection is relatively infrequent in hospitalized patients with COVID-19. The majority of these patients may not require empirical antibacterial treatment.

Clin Microbiol Infect2020       LitCov and CORD-19
1093Hospitality and tourism industry amid COVID-19 pandemic: Perspectives on challenges and learnings from India  

COVID-19 outbreak has presented unprecedented circumstances before the fragile tourism and hospitality industry. The highly infectious novel coronavirus continues to thwart the sector and raises serious questions about the present and future survival of the sector. The study draws on the interviews with 15 participants in senior positions in hospitality industry, and tourism and hospitality education services. Various themes that emerged from the content analysis of interview responses related to the COVID-19 pandemic have been condensed and presented. The dominant themes that emerged out of the qualitative enquiry included need of multiskilling and professional development of the employees, increased sense of hygiene, sanitation and related SOPs, optimism toward rival of the industry, media roles, and need of better crisis preparedness, followed by provisions for reserved funds, adoption of technology in future, costs and expense related aspects etc. The study critically discussed prominent themes in the light of the existing arguments from the literature and reflects on implications for the decision makers. Limitations and scope of future research has also been highlighted.

Int J Hosp Manag2020       LitCov and CORD-19
1094Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant  

BACKGROUND: Assessment of the safety and efficacy of vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in different populations is essential, as is investigation of the efficacy of the vaccines against emerging SARS-CoV-2 variants of concern, including the B.1.351 (501Y.V2) variant first identified in South Africa. METHODS: We conducted a multicenter, double-blind, randomized, controlled trial to assess the safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) in people not infected with the human immunodeficiency virus (HIV) in South Africa. Participants 18 to less than 65 years of age were assigned in a 1:1 ratio to receive two doses of vaccine containing 5×10(10) viral particles or placebo (0.9% sodium chloride solution) 21 to 35 days apart. Serum samples obtained from 25 participants after the second dose were tested by pseudovirus and live-virus neutralization assays against the original D614G virus and the B.1.351 variant. The primary end points were safety and efficacy of the vaccine against laboratory-confirmed symptomatic coronavirus 2019 illness (Covid-19) more than 14 days after the second dose. RESULTS: Between June 24 and November 9, 2020, we enrolled 2026 HIV-negative adults (median age, 30 years); 1010 and 1011 participants received at least one dose of placebo or vaccine, respectively. Both the pseudovirus and the live-virus neutralization assays showed greater resistance to the B.1.351 variant in serum samples obtained from vaccine recipients than in samples from placebo recipients. In the primary end-point analysis, mild-to-moderate Covid-19 developed in 23 of 717 placebo recipients (3.2%) and in 19 of 750 vaccine recipients (2.5%), for an efficacy of 21.9% (95% confidence interval [CI], −49.9 to 59.8). Among the 42 participants with Covid-19, 39 cases (92.9%) were caused by the B.1.351 variant; vaccine efficacy against this variant, analyzed as a secondary end point, was 10.4% (95% CI, −76.8 to 54.8). The incidence of serious adverse events was balanced between the vaccine and placebo groups. CONCLUSIONS: A two-dose regimen of the ChAdOx1 nCoV-19 vaccine did not show protection against mild-to-moderate Covid-19 due to the B.1.351 variant. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT04444674; Pan African Clinical Trials Registry number, PACTR202006922165132).

N Engl J Med2021       LitCov and CORD-19
1095Clinical progression of patients with COVID-19 in Shanghai, China  

BACKGROUND: Studies on the 2019 novel coronavirus disease (COVID-19) have generally been limited to the description of the epidemiology and initial clinical characteristics. We investigated the temporal progression in patients with COVID-19. METHODS: In this retrospective, single-center study, we included confirmed cases of COVID-19 from Jan 20 to Feb 6, 2020 in Shanghai. Final date of follow-up was February 25, 2020. RESULTS: Of the 249 patients enrolled, the median age was 51 years old, and 126 (50.6%) were male. The duration from onset of symptoms to hospitalization was 4(2–7) days in symptomatic patients. Fever was occurred in 235(94.3%) patients. A total of 215 (86.3%) patients had been discharged after 16(12–20) days hospitalization. The estimated median duration of fever in all the patients with fever was 10 days (95 confidential intervals [CIs]: 8–11 days) after onset of symptoms. Patients who were transferred to intensive care units (ICU) had significantly longer duration of fever as compared to those not in ICU (31 days v.s. 9 days after onset of symptoms, respectively, P <0.0001). Radiological aggravation of initial image was observed in 163 (65.7%) patients on day 7 after onset of symptoms. 154(94.5%) of these patients showed radiological improvement on day 14. The median duration to negative reverse-transcriptase PCR tests of upper respiratory tract samples was 11 days (95 CIs: 10–12 days). Viral clearance was more likely to be delayed in patients in ICU than those not in ICU (P <0.0001). In multivariate logistical analysis, age (Odds ratio [OR] = 1.06) and CD4 T cell count (OR = 0.55 per 100 cells/ul increase) were independently associated with ICU admission. CONCLUSIONS: The majority of COVID-19 cases are mild. The clinical progression pattern suggests that early control of viral replication and application of host-directed therapy in later stage is essential to improve the prognosis of CVOID-19.

J Infect2020       LitCov and CORD-19
1096Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases  

BACKGROUND: Cutaneous manifestations of COVID‐19 disease are poorly characterized. OBJECTIVES: To describe the cutaneous manifestations of COVID‐19 disease and to relate them to other clinical findings METHODS: Nationwide case collection survey of images and clinical data. Using a consensus, we described 5 clinical patterns. We later described the association of these patterns with patient demographics, timing in relation to symptoms of the disease, severity, and prognosis. RESULTS: Lesions may be classified as acral areas of erythema with vesicles or pustules (Pseudo‐chilblain) (19%), other vesicular eruptions (9%), urticarial lesions (19%), maculopapular eruptions (47%) and livedo or necrosis (6%). Vesicular eruptions appear early in the course of the disease (15% before other symptoms). The pseudo‐chilblain pattern frequently appears late in the evolution of the COVID‐19 disease (59% after other symptoms), while the rest tend to appear with other symptoms of COVID‐19. Severity of COVID‐19 shows a gradient from less severe disease in acral lesions to most severe in the latter groups. Results are similar for confirmed and suspected cases, both in terms of clinical and epidemiological findings. Alternative diagnoses are discussed but seem unlikely for the most specific patterns (pseudo‐chilblain and vesicular). CONCLUSIONS: We provide a description of the cutaneous manifestations associated with COVID‐19 infection. These may help clinicians approach patients with the disease and recognize paucisymptomatic cases.

Br J Dermatol2020       LitCov and CORD-19
1097The pivotal link between ACE2 deficiency and SARS-CoV-2 infection  

Abstract Angiotensin converting enzyme-2 (ACE2) receptors mediate the entry into the cell of three strains of coronavirus: SARS-CoV, NL63 and SARS-CoV-2. ACE2 receptors are ubiquitous and widely expressed in the heart, vessels, gut, lung (particularly in type 2 pneumocytes and macrophages), kidney, testis and brain. ACE2 is mostly bound to cell membranes and only scarcely present in the circulation in a soluble form. An important salutary function of membrane-bound and soluble ACE2 is the degradation of angiotensin II to angiotensin1-7. Consequently, ACE2 receptors limit several detrimental effects resulting from binding of angiotensin II to AT1 receptors, which include vasoconstriction, enhanced inflammation and thrombosis. The increased generation of angiotensin1-7 also triggers counter-regulatory protective effects through binding to G-protein coupled Mas receptors. Unfortunately, the entry of SARS-CoV2 into the cells through membrane fusion markedly down-regulates ACE2 receptors, with loss of the catalytic effect of these receptors at the external site of the membrane. Increased pulmonary inflammation and coagulation have been reported as unwanted effects of enhanced and unopposed angiotensin II effects via the ACE→Angiotensin II→AT1 receptor axis. Clinical reports of patients infected with SARS-CoV-2 show that several features associated with infection and severity of the disease (i.e., older age, hypertension, diabetes, cardiovascular disease) share a variable degree of ACE2 deficiency. We suggest that ACE2 down-regulation induced by viral invasion may be especially detrimental in people with baseline ACE2 deficiency associated with the above conditions. The additional ACE2 deficiency after viral invasion might amplify the dysregulation between the ‘adverse’ ACE→Angiotensin II→AT1 receptor axis and the ‘protective’ ACE2→Angiotensin1-7→Mas receptor axis. In the lungs, such dysregulation would favor the progression of inflammatory and thrombotic processes triggered by local angiotensin II hyperactivity unopposed by angiotensin1-7. In this setting, recombinant ACE2, angiotensin1-7 and angiotensin II type 1 receptor blockers could be promising therapeutic approaches in patients with SARS-CoV-2 infection.

Eur J Intern Med2020       LitCov and CORD-19
1098Engineering strategies to overcome the current roadblocks in CAR T-cell therapy  

T cells genetically engineered to express chimeric antigen receptors (CARs) have proven — and impressive — therapeutic activity in patients with certain subtypes of B cell leukaemia or lymphoma, with promising efficacy also demonstrated in patients with multiple myeloma. Nevertheless, various barriers restrict the efficacy and/or prevent the widespread use of CAR T cell therapies in these patients as well as in those with other cancers, particularly solid tumours. Key challenges relating to CAR T cells include severe toxicities, restricted trafficking to, infiltration into and activation within tumours, suboptimal persistence in vivo, antigen escape and heterogeneity, and manufacturing issues. The evolution of CAR designs beyond the conventional structures will be necessary to address these limitations and to expand the use of CAR T cells to a wider range of malignancies. Investigators are addressing the current obstacles with a wide range of engineering strategies in order to improve the safety, efficacy and applicability of this therapeutic modality. In this Review, we discuss the innovative designs of novel CAR T cell products that are being developed to increase and expand the clinical benefits of these treatments in patients with diverse cancers.

Nat Rev Clin Oncol2019       CORD-19
1099Maternal and Neonatal Morbidity and Mortality Among Pregnant Women With and Without COVID-19 Infection: The INTERCOVID Multinational Cohort Study  

IMPORTANCE: Detailed information about the association of COVID-19 with outcomes in pregnant individuals compared with not-infected pregnant individuals is much needed. OBJECTIVE: To evaluate the risks associated with COVID-19 in pregnancy on maternal and neonatal outcomes compared with not-infected, concomitant pregnant individuals. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study that took place from March to October 2020, involving 43 institutions in 18 countries, 2 unmatched, consecutive, not-infected women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge. EXPOSURES: COVID-19 in pregnancy determined by laboratory confirmation of COVID-19 and/or radiological pulmonary findings or 2 or more predefined COVID-19 symptoms. MAIN OUTCOMES AND MEASURES: The primary outcome measures were indices of (maternal and severe neonatal/perinatal) morbidity and mortality; the individual components of these indices were secondary outcomes. Models for these outcomes were adjusted for country, month entering study, maternal age, and history of morbidity. RESULTS: A total of 706 pregnant women with COVID-19 diagnosis and 1424 pregnant women without COVID-19 diagnosis were enrolled, all with broadly similar demographic characteristics (mean [SD] age, 30.2 [6.1] years). Overweight early in pregnancy occurred in 323 women (48.6%) with COVID-19 diagnosis and 554 women (40.2%) without. Women with COVID-19 diagnosis were at higher risk for preeclampsia/eclampsia (relative risk [RR], 1.76; 95% CI, 1.27-2.43), severe infections (RR, 3.38; 95% CI, 1.63-7.01), intensive care unit admission (RR, 5.04; 95% CI, 3.13-8.10), maternal mortality (RR, 22.3; 95% CI, 2.88-172), preterm birth (RR, 1.59; 95% CI, 1.30-1.94), medically indicated preterm birth (RR, 1.97; 95% CI, 1.56-2.51), severe neonatal morbidity index (RR, 2.66; 95% CI, 1.69-4.18), and severe perinatal morbidity and mortality index (RR, 2.14; 95% CI, 1.66-2.75). Fever and shortness of breath for any duration was associated with increased risk of severe maternal complications (RR, 2.56; 95% CI, 1.92-3.40) and neonatal complications (RR, 4.97; 95% CI, 2.11-11.69). Asymptomatic women with COVID-19 diagnosis remained at higher risk only for maternal morbidity (RR, 1.24; 95% CI, 1.00-1.54) and preeclampsia (RR, 1.63; 95% CI, 1.01-2.63). Among women who tested positive (98.1% by real-time polymerase chain reaction), 54 (13%) of their neonates tested positive. Cesarean delivery (RR, 2.15; 95% CI, 1.18-3.91) but not breastfeeding (RR, 1.10; 95% CI, 0.66-1.85) was associated with increased risk for neonatal test positivity. CONCLUSIONS AND RELEVANCE: In this multinational cohort study, COVID-19 in pregnancy was associated with consistent and substantial increases in severe maternal morbidity and mortality and neonatal complications when pregnant women with and without COVID-19 diagnosis were compared. The findings should alert pregnant individuals and clinicians to implement strictly all the recommended COVID-19 preventive measures.

JAMA Pediatr2021       LitCov and CORD-19
1100Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China: Dong Y, Mo X, Hu Y, et al. Pediatrics. 2020; doi: 10.1542/peds.2020-0702  

J Emerg Med2020       CORD-19

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(3) Currently tweets of June 23rd to June 29th 2022 have been considered.

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