|1||Beyond the black stump: rapid reviews of health research issues affecting regional, rural and remote Australia |
|Med J Aust||2020||CORD-19|
|2||Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China |
Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
|Lancet||2020||LitCov and CORD-19|
|3||Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study |
BACKGROUND: Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. METHODS: In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. FINDINGS: 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. INTERPRETATION: The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. FUNDING: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
|Lancet||2020||LitCov and CORD-19|
|4||Clinical Characteristics of COVID-19 in China |
BACKGROUND: Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. METHODS: We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. RESULTS: The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. CONCLUSIONS: During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
|N Engl J Med||2020||LitCov and CORD-19|
|5||Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China |
|JAMA||2020||LitCov and CORD-19|
|6||A novel coronavirus associated with severe acute respiratory syndrome |
|N Engl J Med||2003||CORD-19|
|7||Identification of a novel coronavirus in patients with severe acute respiratory syndrome |
|N Engl J Med||2003||CORD-19|
|8||A Novel Coronavirus from Patients with Pneumonia in China, 2019 |
In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)
|N Engl J Med||2020||LitCov and CORD-19|
|9||Epidemiological and clinical characteristics of coronavirus disease cases at a screening clinic during the early outbreak period: a single-center study |
INTRODUCTION. Coronavirus disease 2019 (COVID-19) is an infectious disease caused by Severe Acute Respiratory Corona Virus-2 (SARS-CoV-2). The disease was first identified in December 2019 in Wuhan, the capital of China's Hubei province, and has since spread globally, resulting in the ongoing 2019–2020 corona virus pandemic. SARS-CoV-2 is closely related to the original SARS-CoV. It is thought to have a zoonotic origin. The virus is primarily spread between people during close contact, often via small droplets produced by coughing, sneezing or talking. People may also become infected by touching a contaminated surface and then touching their face. COVID-19 patients currently remain the primary source of infection. An epidemiological survey indicated that the general population is susceptible to SARS-CoV-2. The spectrum of this disease ranges from mild to life-threatening. Fever is the most common symptom, although older people and those with comorbidities may experience fever later in the disease. Other common symptoms include cough, loss of appetite, fatigue, shortness of breath, sputum production, and muscle and joint pains. Symptoms such as nausea, vomiting and diarrhea have been observed in varying percentages. Some cases might progress promptly to acute respiratory distress syndrome (ARDS) and/or multiple organ function failure. Asymptomatic carriers and those in the incubation period may also be infectious. AIM. To determine the epidemiological and clinical characteristics of patients presenting with COVID-19 at the screening clinic of a tertiary care hospital in Peshawar, Pakistan. METHODOLOGY. In this descriptive study, we analysed data of patients presenting to a newly established Covid-19 screening clinic in Rehman Medical Institute. Anyone who reported with new onset fever and/or cough was tested for SARS-CoV-2 in the screening clinic. We documented and analysed demographic, epidemiological and clinical characteristics, which included age, sex, travel history, clinical features, comorbidities and laboratory data of patients confirmed by real-time reverse-transcription (RT)-PCR at Rehman Medical Institute, Peshawar, Pakistan from 15 March till 21 April 2020. Paired specimens of throat swabs and nasal swabs were obtained from 845 patients, ribonucleic acid (RNA) was extracted and tested for SARS-CoV-2 by the RT-PCR assay. RESULTS. A total of 845 specimens were taken as described above. The positive rate for SARS-CoV-2 was about 14.3%. Male and older population had a significantly higher positive rate. Of the 121 patients infected with SARS-CoV-2, the mean age was 43.19 years (sd, 17.57) and the infections were more frequent among male gender accounting for 85 (70.25 %) patients. Common symptoms included fever (88 patients, 72 %), cough (72 patients, 59.5 %) and shortness of breath (69 patients, 57 %). Twenty-two (18 %) patients had recent travel history outside Pakistan in the previous 14 days, the majority of whom had returned back from Saudi Arabia. CONCLUSION. In this single-centre, prospective, descriptive study, fever, cough and shortness of breath were the most common symptoms. Old age (>50 years), chronic underlying comorbidities and travel history may be risk factors. Therefore, we concluded that viral nucleic acid amplification tests (NAAT) played an important role in identifying SARS-CoV-2 infection in a screening clinic, which helped with isolation and cohorting of these patients.
|J Med Microbiol||2020||LitCov and CORD-19|
|10||Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study |
BACKGROUND: In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. METHODS: In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. FINDINGS: Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. INTERPRETATION: The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. FUNDING: National Key R&D Program of China.
|Lancet||2020||LitCov and CORD-19|
|11||Health professionals facing the COVID-19 pandemic: What are the mental health risks? |
RÉSUMÉ Objectifs: La pandémie de la maladie à coronavirus (COVID-19) a provoqué une crise sanitaire majeure et mis en quarantaine la moitié de la population planétaire. En France, elle a provoqué une réorganisation en urgence de l’offre de soins mobilisant les soignants dans un climat d’incertitude. L'objectif du présent article est de faire le point sur les risques associés à l’exposition des soignants au COVID-19 pour leur santé mentale. Méthodes: Les auteurs ont conduit une revue de la littérature internationale tenant compte des données des précédentes épidémies (SARS-CoV-1, H1N1) et des données plus récentes concernant le COVID-19. Résultats: Les caractéristiques de cette pandémie (rapidité de diffusion, connaissances incertaines, sévérité, morts de soignants) ont installé un climat anxiogène. Des facteurs organisationnels peuvent être source de stress : déficit d’équipement de protection individuel, réaffectation de postes, manque de communication, manque de matériels de soins, bouleversement de la vie quotidienne familiale et sociale. D’autres facteurs de risque sont identifiés comme l’absence de soutien, la crainte de contaminer un proche, l’isolement ou la stigmatisation sociale, le haut niveau de stress au travail, ou les patterns d’attachement insécure. Les soignants ont ainsi un risque augmenté d’anxiété, de dépression, d’épuisement, d’addiction et de trouble de stress post-traumatique. Conclusions: Cette crise sanitaire devrait nous aider à mieux comprendre la vulnérabilité des soignants à la souffrance psychologique afin de renforcer les stratégies de prévention primaire et la formation aux enjeux psychologiques des soins, de la relation, et de la gestion des situations de crises sanitaires. ABSTRACT Objectives: The coronavirus disease 2019 (COVID-19) pandemic has caused major sanitary crisis worldwide. Half of the world has been placed in quarantine. In France, this large-scale health crisis urgently triggered the restructuring and reorganization of health service delivery to support emergency services, medical intensive care units and continuing care units. Health professionals mobilized all their resources to provide emergency aid in a general climate of uncertainty. Concerns about the mental health, psychological adjustment, and recovery of health care workers treating and caring for patients with COVID-19 are now arising. The goal of the present article is to provide an up-to-date information on potential mental health risks associated with exposure of health professionals to the COVID-19 pandemic. Methods: Authors performed a narrative review identifying relevant results in the scientific and medical literature considering previous epidemics of 2003 (SARS-CoV-1) and 2009 (H1N1) with the more recent data about the COVID-19 pandemic. We highlighted most relevant data concerning the disease characteristics, the organizational factors and personal factors that may contribute to developing psychological distress and other mental health symptoms. Results: The disease characteristics of the current COVID-19 pandemic provoked a generalized climate of wariness and uncertainty, particularly among health professionals, due to a range of causes such as the rapid spread of COVID-19, the severity of symptoms it can cause in a segment of infected individuals, the lack of knowledge of the disease, and deaths among health professionals. Stress may also be caused by organizational factors, such as depletion of personal protection equipment, concern about not being able to provide competent care if deployed to new area, concern about rapidly changing information, lack of access to up-to-date information and communication, lack of specific drugs, the shortage of ventilators and intensive care unit beds necessary to care for the surge of critically ill patients, and significant change in their daily social and family life. Further risk factors have been identified, including feelings of being inadequately supported, concerns about health of self, fear of taking home infection to family members or others, and not having rapid access to testing through occupational health if needed, being isolated, feelings of uncertainty and social stigmatization, overwhelming workload, or insecure attachment. Additionally, we discussed positive social and organizational factors that contribute to enhance resilience in the face of the pandemic. There is a consensus in all the relevant literature that health care professionals are at an increased risk of high levels of stress, anxiety, depression, burnout, addiction and post-traumatic stress disorder, which could have long-term psychological implications. Conclusions: In the long run, this tragic health crisis should significantly enhance our understanding of the mental health risk factors among the health care professionals facing the COVID-19 pandemic. Reporting information such as this is essential to plan future prevention strategies. Protecting health care professionals is indeed an important component of public health measures to address large-scale health crisis. Thus, interventions to promote mental well-being in health care professionals exposed to COVID-19 need to be immediately implemented, and to strengthen prevention and response strategies by training health care professionals on mental help and crisis management.
|Encephale||2020||LitCov and CORD-19|
|12||Characterization of a novel coronavirus associated with severe acute respiratory syndrome |
|13||Characteristics of and Important Lessons From the COVID-19 Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention |
|JAMA||2020||LitCov and CORD-19|
|14||The Genome sequence of the SARS-associated coronavirus |
|15||A pneumonia outbreak associated with a new coronavirus of probable bat origin |
Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats(1–4). Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans(5–7). Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
|Nature||2020||LitCov and CORD-19|
|16||Safety and Efficacy of Imatinib for Hospitalized Adults with COVID-19: A structured summary of a study protocol for a randomised controlled trial |
OBJECTIVES: Primary Objective: To evaluate the efficacy and safety of oral administration of imatinib combined with the Best Conventional Care (BCC) versus placebo plus BCC in hospitalized patients with COVID-19. Hypothesis: Addition of imatinib to the BCC will provide a superior clinical outcome for patients with COVID-19 compared with BCC plus placebo. This hypothesis is on the basis of 1) intralysosomal entrapment of imatinib will increase endosomal pH and effectively decrease SARS-CoV-2/cell fusion, 2) kinase inhibitory activity of imatinib will interfere with budding/release or replication of SARS-CoV-2, and 3) because of the critical role of mechanical ventilation in the care of patients with ARDS, imatinib will have a significant clinical impact for patients with critical COVID-19 infection in Intensive Care Unit (ICU). TRIAL DESIGN: This is an individual patient-level randomized, double-blind, placebo-controlled, two-parallel arm phase 3 study to evaluate the safety and efficacy of imatinib for the treatment of hospitalized adults with COVID-19. Participants will be followed for up to 60 days from the start of study drug administration. This trial will be conducted in accordance with the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines of the International Conference on Harmonization. PARTICIPANTS: Inclusion Criteria: Patients may be included in the study only if they meet all of the following criteria: 1) Ability to understand and willingness to sign a written informed consent document. Informed consent must be obtained prior to participation in the study. For patients who are too unwell to provide consent such as patients on invasive ventilator or extracorporeal membrane oxygenation (ECMO), their Legally Authorized Representative (LAR) can sign the informed consent, 2) Hospitalized patients ≥18 years of age, 3) Positive reverse transcriptase-polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 in the respiratory tract sample (oropharyngeal, nasopharyngeal or bronchoalveolar lavage (BAL)) by Center for Disease Control or local laboratory within 7 days of randomization, 4) Women of childbearing potential must agree to use at least one primary form of contraception for the duration of the study. Exclusion Criteria: Patients meeting any of the following criteria are not eligible for the study: 1) Patients receiving any other investigational agents in a clinical trial. Off-label use of agents such as hydroxychloroquine is not an exclusion criterion, 2) Pregnant or breastfeeding women, 3) Patients with significant liver or renal dysfunction at the time of screening as defined as: 3.1) Direct bilirubin >2.5 mg/dL, 3.2) AST, ALT, or alkaline phosphatase >5x upper limit of normal, 3.3) eGFR ≤30 mL/min or requiring renal replacement therapy, 4) Patients with significant hematologic disorder at screen as defined as: 4.1) Absolute neutrophil count (ANC) <500/μL, 4.2) Platelet <20,000/μL, 4.3) Hemoglobin <7 g/dL, 5) Uncontrolled underlying illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled active seizure disorder, or psychiatric illness/social situations that per site Principal Investigator’s judgment would limit compliance with study requirements, 6) Known allergy to imatinib or its component products, 7) Any other clinical conditions that in the opinion of the investigator would make the subject unsuitable for the study. Both men and women of all races and ethnic groups are eligible for this trial. University of Maryland Medical Center, Baltimore, MD is the initiating site. The study may be opened in other centers on the basis of the accrual rate or the magnitude of the COVID-19 pandemic. INTERVENTION AND COMPARATOR: Imatinib: All doses of imatinib should be administered with a meal and a large glass of water. Imatinib can be dissolved in water or apple juice for patients having difficulty swallowing. In this study, patients with confirmed positive COVID-19 tests receive imatinib for a total of 14 days; 400 mg orally daily Days 1-14. Imatinib 400 mg tablets will be encapsulated using size 000 capsules and cellulose microcrystalline filler. For patients on ventilator or ECMO, imatinib will be given as oral suspension (40 mg/mL). To make the oral suspension, imatinib tablets will be crushed and mixed in Ora-sweet solution to yield a concentration of 40 mg/mL suspension by pharmacy. Additionally, in the absence of supportive microbiological testing results, we confirm that the in-use stability period for the prepared imatinib suspensions will be 24 hours at room temperature or 7 days at refrigerated conditions. The pharmacy staff will follow the American Society Health-System Pharmacists (ASHP) guidelines for handling hazardous drugs. Placebo: The matching placebo will be packaged by Investigational Drug Service Pharmacy at University of Maryland Medical Center. The placebos will be prepared using size 000 capsules and cellulose microcrystalline filler. Imatinib 400 mg capsules and placebo capsules will be identical form and color. For patients on ventilator or ECMO, placebo will be given as oral suspension with similar process for making imatinib suspension. Concomitant Medications/supportive care: In both arms, patients can receive concomitant available local standard of care antipyretics, antibacterials, antivirals, antifungals and anti-inflammatory including hydroxychloroquine at the discretion of the treating physician as necessary. For other drug-drug interactions particularly with CYP P450, the treating physician should consider the risk and benefit of drug administration based on available information. Co-administration of off-label immunomodulatory treatments for COVID-19 including but not limited to corticosteroids, sarilumab, clazakizumab, tocilizumab, and anakinra will be allowed but may affect interpretability of study outcomes. The timing, dosing, and duration of these treatments will be meticulously collected, including any of these treatments that may be used for participants who experience progression of COVID-19 disease after study enrollment. Two analyses will be performed, the primary analysis will compare the primary endpoint in the two trial arms irrespective of any other treatment; the second analysis will be stratified for co-administration of immunomodulatory drugs. MAIN OUTCOMES: The primary endpoint is the proportion of patients with a two-point improvement at Day 14 from baseline using the 8-category ordinal scale. The ordinal scale is an evaluation of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen – no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 8) Death. The secondary endpoints include: All-cause mortality at Day 28, All-cause mortality at Day 60, Time to a 2-point clinical improvement difference over baseline, Duration of hospitalization, Duration of ECMO or invasive mechanical ventilation (for subjects who are on ECMO or mechanical ventilation at Day 1), Duration of ICU stay (for subjects who are in ICU at Day 1), Time to SARS-CoV-2 negative by RT-PCR, Proportion of patients with negative oropharyngeal or nasopharyngeal swab for SARS-CoV-2 by RT-PCR on days 5, 10, 14, 21, and 28 after starting treatment, Proportion of subjects with serious adverse events, Proportion of subjects who discontinue study drug due to adverse events. The exploratory endpoints include: Determine the impact of treatment arms on IL-6 levels, Obtain blood/peripheral blood mononuclear cells (PBMCs) for storage to look at transcriptomics in severe disease, Association of major histocompatibility complex (MHC) with severity of illness, Mean change in the ordinal scale from baseline, Time to an improvement of one category from admission using an ordinal scale, Duration of hospitalization, Duration of new oxygen use, Number of oxygenation free days, Duration of new mechanical ventilation, Number of ventilator free days. RANDOMIZATION: Eligible patients will be uniformly randomized in 1:1 ratio to receive either imatinib or placebo for 14 days. Both groups will receive the BCC. The randomized treatment allocations use stratified, permuted block randomization with a variable block size; blocks are generated using a validated random number generator. In order to balance the severity of the respiratory illness between the two arms, randomization will be stratified based on radiographic findings and oxygen requirements: 1) Severe disease: evidence of pneumonia on chest X-ray or CT scan OR chest auscultation (rales, crackles), and SpO(2) ≤92% on ambient air or PaO(2)/FiO(2) <300 mmHg, and requires supplemental oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device; 2) Critical disease: requires supplemental oxygen delivered by non-rebreather mask or high flow cannula OR use of invasive or non-invasive ventilation OR requiring treatment in an intensive care unit, use of vasopressors, extracorporeal life support, or renal replacement therapy. BLINDING (MASKING): The participants, caregivers, and the statistician are blinded to group assignment. The only people who are not blinded are Site Pharmacists. Blinding will be performed via a specific randomization process. Centralized, concealed randomization will be executed by the Primary Site’s Pharmacist. Data on eligible consented cases will be submitted electronically on the appropriate on-study form to the pharmacy, where the patient is randomized to imatinib or placebo. Imatinib 400 mg capsules and placebo capsules will be identical form and color. For patients on ventilator or ECMO, placebo will be given as oral suspension with similar process for making imatinib suspension. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): The trial is designed as a double-blind, two-parallel arm, randomized controlled trial with a uniform (1:1) allocation ratio to: Arm A) Imatinib or Arm B) Placebo. Patients in both arms will receive the BCC per local institutional standards at the discretion of the treating physician. Group sample sizes of 102 in Arm A and 102 in Arm B achieve 80.6% power to detect a difference between the group proportions of 0.20. The proportion in Arm A (imatinib treatment arm) is assumed to be 0.30 under the null hypothesis and 0.50 under the alternative hypothesis. The proportion in Arm B (placebo control arm) is 0.30. The test statistic used is the two-sided Fisher's Exact Test. The significance level of the test is targeted at 0.05. The significance level actually achieved by this design is α=0.0385. The power of the test is calculated using binomial enumeration of all possible outcomes. The primary analysis will be conducted using an intention to treat principle (ITT) for participants who at least receive one dose of study drug or placebo. The sample size is not inflated for dropouts. All patients will be evaluable irrespective of the clinical course of their disease. TRIAL STATUS: Current protocol version is 1.2 from May 8, 2020. The recruitment started on June 15, 2020 and is ongoing. We originally anticipated that the trial would finish recruitment by mid 2021. We are aware of the enrollment requirement of approximately 200 patients, which is required to provide scientific integrity of the results. We are also aware of the fact that enrolling this number of patients in a single-site at University of Maryland Medical Center (UMMC) may take longer than expected, particularly taken into account other competing studies. For this reason, we are actively considering opening the protocol in other sites. After identification of other sites, we will fulfill all regulatory requirements before opening the protocol in other sites. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04394416. First Posted: May 19, 2020; Last Update Posted: June 4, 2020. FDA has issued the “Study May Proceed” Letter for this clinical trial under the Investigational New Drug (IND) number 149239. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. SUPPLEMENTARY INFORMATION: Supplementary information accompanies this paper at 10.1186/s13063-020-04819-9.
|Trials||2020||LitCov and CORD-19|
|17||Travel-related control measures to contain the COVID-19 pandemic: a rapid review |
|Cochrane Database Syst Rev||2020||LitCov and CORD-19|
|18||Coronavirus 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.
|19||Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia |
BACKGROUND: The initial cases of novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP. METHODS: We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number. RESULTS: Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9). CONCLUSIONS: On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.)
|N Engl J Med||2020||LitCov and CORD-19|
|20||Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus |
Spike (S) proteins of coronaviruses, including the coronavirus that causes severe acute respiratory syndrome (SARS), associate with cellular receptors to mediate infection of their target cells(1,2). Here we identify a metallopeptidase, angiotensin-converting enzyme 2 (ACE2)(3,4), isolated from SARS coronavirus (SARS-CoV)-permissive Vero E6 cells, that efficiently binds the S1 domain of the SARS-CoV S protein. We found that a soluble form of ACE2, but not of the related enzyme ACE1, blocked association of the S1 domain with Vero E6 cells. 293T cells transfected with ACE2, but not those transfected with human immunodeficiency virus-1 receptors, formed multinucleated syncytia with cells expressing S protein. Furthermore, SARS-CoV replicated efficiently on ACE2-transfected but not mock-transfected 293T cells. Finally, anti-ACE2 but not anti-ACE1 antibody blocked viral replication on Vero E6 cells. Together our data indicate that ACE2 is a functional receptor for SARS-CoV. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature02145) contains supplementary material, which is available to authorized users.
|21||SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor |
The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
|Cell||2020||LitCov and CORD-19|
|22||Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy |
|JAMA||2020||LitCov and CORD-19|
|23||Rapid, point-of-care antigen and molecular-based tests for diagnosis of SARS-CoV-2 infection |
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and the resulting COVID‐19 pandemic present important diagnostic challenges. Several diagnostic strategies are available to identify or rule out current infection, identify people in need of care escalation, or to test for past infection and immune response. Point‐of‐care antigen and molecular tests to detect current SARS‐CoV‐2 infection have the potential to allow earlier detection and isolation of confirmed cases compared to laboratory‐based diagnostic methods, with the aim of reducing household and community transmission. OBJECTIVES: To assess the diagnostic accuracy of point‐of‐care antigen and molecular‐based tests to determine if a person presenting in the community or in primary or secondary care has current SARS‐CoV‐2 infection. SEARCH METHODS: On 25 May 2020 we undertook electronic searches in the Cochrane COVID‐19 Study Register and the COVID‐19 Living Evidence Database from the University of Bern, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we checked repositories of COVID‐19 publications. We did not apply any language restrictions. SELECTION CRITERIA: We included studies of people with suspected current SARS‐CoV‐2 infection, known to have, or not to have SARS‐CoV‐2 infection, or where tests were used to screen for infection. We included test accuracy studies of any design that evaluated antigen or molecular tests suitable for a point‐of‐care setting (minimal equipment, sample preparation, and biosafety requirements, with results available within two hours of sample collection). We included all reference standards to define the presence or absence of SARS‐CoV‐2 (including reverse transcription polymerase chain reaction (RT‐PCR) tests and established clinical diagnostic criteria). DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies and resolved any disagreements by discussion with a third review author. One review author independently extracted study characteristics, which were checked by a second review author. Two review authors independently extracted 2x2 contingency table data and assessed risk of bias and applicability of the studies using the QUADAS‐2 tool. We present sensitivity and specificity, with 95% confidence intervals (CIs), for each test using paired forest plots. We pooled data using the bivariate hierarchical model separately for antigen and molecular‐based tests, with simplifications when few studies were available. We tabulated available data by test manufacturer. MAIN RESULTS: We included 22 publications reporting on a total of 18 study cohorts with 3198 unique samples, of which 1775 had confirmed SARS‐CoV‐2 infection. Ten studies took place in North America, two in South America, four in Europe, one in China and one was conducted internationally. We identified data for eight commercial tests (four antigen and four molecular) and one in‐house antigen test. Five of the studies included were only available as preprints. We did not find any studies at low risk of bias for all quality domains and had concerns about applicability of results across all studies. We judged patient selection to be at high risk of bias in 50% of the studies because of deliberate over‐sampling of samples with confirmed COVID‐19 infection and unclear in seven out of 18 studies because of poor reporting. Sixteen (89%) studies used only a single, negative RT‐PCR to confirm the absence of COVID‐19 infection, risking missing infection. There was a lack of information on blinding of index test (n = 11), and around participant exclusions from analyses (n = 10). We did not observe differences in methodological quality between antigen and molecular test evaluations. Antigen tests Sensitivity varied considerably across studies (from 0% to 94%): the average sensitivity was 56.2% (95% CI 29.5 to 79.8%) and average specificity was 99.5% (95% CI 98.1% to 99.9%; based on 8 evaluations in 5 studies on 943 samples). Data for individual antigen tests were limited with no more than two studies for any test. Rapid molecular assays Sensitivity showed less variation compared to antigen tests (from 68% to 100%), average sensitivity was 95.2% (95% CI 86.7% to 98.3%) and specificity 98.9% (95% CI 97.3% to 99.5%) based on 13 evaluations in 11 studies of on 2255 samples. Predicted values based on a hypothetical cohort of 1000 people with suspected COVID‐19 infection (with a prevalence of 10%) result in 105 positive test results including 10 false positives (positive predictive value 90%), and 895 negative results including 5 false negatives (negative predictive value 99%). Individual tests We calculated pooled results of individual tests for ID NOW (Abbott Laboratories) (5 evaluations) and Xpert Xpress (Cepheid Inc) (6 evaluations). Summary sensitivity for the Xpert Xpress assay (99.4%, 95% CI 98.0% to 99.8%) was 22.6 (95% CI 18.8 to 26.3) percentage points higher than that of ID NOW (76.8%, (95% CI 72.9% to 80.3%), whilst the specificity of Xpert Xpress (96.8%, 95% CI 90.6% to 99.0%) was marginally lower than ID NOW (99.6%, 95% CI 98.4% to 99.9%; a difference of −2.8% (95% CI −6.4 to 0.8)) AUTHORS' CONCLUSIONS: This review identifies early‐stage evaluations of point‐of‐care tests for detecting SARS‐CoV‐2 infection, largely based on remnant laboratory samples. The findings currently have limited applicability, as we are uncertain whether tests will perform in the same way in clinical practice, and according to symptoms of COVID‐19, duration of symptoms, or in asymptomatic people. Rapid tests have the potential to be used to inform triage of RT‐PCR use, allowing earlier detection of those testing positive, but the evidence currently is not strong enough to determine how useful they are in clinical practice. Prospective and comparative evaluations of rapid tests for COVID‐19 infection in clinically relevant settings are urgently needed. Studies should recruit consecutive series of eligible participants, including both those presenting for testing due to symptoms and asymptomatic people who may have come into contact with confirmed cases. Studies should clearly describe symptomatic status and document time from symptom onset or time since exposure. Point‐of‐care tests must be conducted on samples according to manufacturer instructions for use and be conducted at the point of care. Any future research study report should conform to the Standards for Reporting of Diagnostic Accuracy (STARD) guideline.
|Cochrane Database Syst Rev||2020||LitCov and CORD-19|
|24||Building a sustainable rural physician workforce |
|Med J Aust||2021||CORD-19|
|25||Prevalence of and Risk Factors Associated With Mental Health Symptoms Among the General Population in China During the COVID-19 Pandemic |
IMPORTANCE: People exposed to coronavirus disease 2019 (COVID-19) and a series of imperative containment measures could be psychologically stressed, yet the burden of and factors associated with mental health symptoms remain unclear. OBJECTIVE: To investigate the prevalence of and risk factors associated with mental health symptoms in the general population in China during the COVID-19 pandemic. DESIGN, SETTING, AND PARTICIPANTS: This large-sample, cross-sectional, population-based, online survey study was conducted from February 28, 2020, to March 11, 2020. It involved all 34 province-level regions in China and included participants aged 18 years and older. Data analysis was performed from March to May 2020. MAIN OUTCOMES AND MEASURES: The prevalence of symptoms of depression, anxiety, insomnia, and acute stress among the general population in China during the COVID-19 pandemic was evaluated using the Patient Health Questionnaire–9, Generalized Anxiety Disorder–7, Insomnia Severity Index, and Acute Stress Disorder Scale. Logistic regression analyses were used to explore demographic and COVID-19–related risk factors. RESULTS: Of 71 227 individuals who clicked on the survey link, 56 932 submitted the questionnaires, for a participation rate of 79.9%. After excluding the invalid questionnaires, 56 679 participants (mean [SD] age, 35.97 [8.22] years; 27 149 men [47.9%]) were included in the study; 39 468 respondents (69.6%) were aged 18 to 39 years. During the COVID-19 pandemic, the rates of mental health symptoms among the survey respondents were 27.9% (95% CI, 27.5%-28.2%) for depression, 31.6% (95% CI, 31.2%-32.0%) for anxiety, 29.2% (95% CI, 28.8%-29.6%) for insomnia, and 24.4% (95% CI, 24.0%-24.7%) for acute stress. Participants with confirmed or suspected COVID-19 and their family members or friends had a high risk for symptoms of depression (adjusted odds ratios [ORs], 3.27 [95% CI, 1.84-5.80] for patients; 1.53 [95% CI, 1.26-1.85] for family or friends), anxiety (adjusted ORs, 2.48 [95% CI, 1.43-4.31] for patients; 1.53 [95% CI, 1.27-1.84] for family or friends), insomnia (adjusted ORs, 3.06 [95% CI, 1.73-5.43] for patients; 1.62 [95% CI, 1.35-1.96] for family or friends), and acute stress (adjusted ORs, 3.50 [95% CI, 2.02-6.07] for patients; 1.77 [95% CI, 1.46-2.15] for family or friends). Moreover, people with occupational exposure risks and residents in Hubei province had increased odds of symptoms of depression (adjusted ORs, 1.96 [95% CI, 1.77-2.17] for occupational exposure; 1.42 [95% CI, 1.19-1.68] for Hubei residence), anxiety (adjusted ORs, 1.93 [95% CI, 1.75-2.13] for occupational exposure; 1.54 [95% CI, 1.30-1.82] for Hubei residence), insomnia (adjusted ORs, 1.60 [95% CI, 1.45-1.77] for occupational exposure; 1.20 [95% CI, 1.01-1.42] for Hubei residence), and acute stress (adjusted ORs, 1.98 [95% CI, 1.79-2.20] for occupational exposure; 1.49 [95% CI, 1.25-1.79] for Hubei residence). Both centralized quarantine (adjusted ORs, 1.33 [95% CI, 1.10-1.61] for depression; 1.46 [95% CI, 1.22-1.75] for anxiety; 1.63 [95% CI, 1.36-1.95] for insomnia; 1.46 [95% CI, 1.21-1.77] for acute stress) and home quarantine (adjusted ORs, 1.30 [95% CI, 1.25-1.36] for depression; 1.28 [95% CI, 1.23-1.34] for anxiety; 1.24 [95% CI, 1.19-1.30] for insomnia; 1.29 [95% CI, 1.24-1.35] for acute stress) were associated with the 4 negative mental health outcomes. Being at work was associated with lower risks of depression (adjusted OR, 0.85 [95% CI, 0.79-0.91]), anxiety (adjusted OR, 0.92 [95% CI, 0.86-0.99]), and insomnia (adjusted OR, 0.87 [95% CI, 0.81-0.94]). CONCLUSIONS AND RELEVANCE: The results of this survey indicate that mental health symptoms may have been common during the COVID-19 outbreak among the general population in China, especially among infected individuals, people with suspected infection, and people who might have contact with patients with COVID-19. Some measures, such as quarantine and delays in returning to work, were also associated with mental health among the public. These findings identify populations at risk for mental health problems during the COVID-19 pandemic and may help in implementing mental health intervention policies in other countries and regions.
|JAMA Netw Open||2020||LitCov and CORD-19|
|26||A Practical Approach to the Management of Cancer Patients During the Novel COVID-19 Pandemic: An International Collaborative Group |
The outbreak of coronavirus disease 2019 (COVID‐19) has rapidly spread globally since being identified as a public health emergency of major international concern and has now been declared a pandemic by the World Health Organization (WHO). In December 2019, an outbreak of atypical pneumonia, known as COVID‐19, was identified in Wuhan, China. The newly identified zoonotic coronavirus, severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), is characterized by rapid human‐to‐human transmission. Many cancer patients frequently visit the hospital for treatment and disease surveillance. They may be immunocompromised due to the underlying malignancy or anticancer therapy and are at higher risk of developing infections. Several factors increase the risk of infection, and cancer patients commonly have multiple risk factors. Cancer patients appear to have an estimated twofold increased risk of contracting SARS‐CoV‐2 than the general population. With the WHO declaring the novel coronavirus outbreak a pandemic, there is an urgent need to address the impact of such a pandemic on cancer patients. This include changes to resource allocation, clinical care, and the consent process during a pandemic. Currently and due to limited data, there are no international guidelines to address the management of cancer patients in any infectious pandemic. In this review, the potential challenges associated with managing cancer patients during the COVID‐19 infection pandemic will be addressed, with suggestions of some practical approaches. IMPLICATIONS FOR PRACTICE: The main management strategies for treating cancer patients during the COVID‐19 epidemic include clear communication and education about hand hygiene, infection control measures, high‐risk exposure, and the signs and symptoms of COVID‐19. Consideration of risk and benefit for active intervention in the cancer population must be individualized. Postponing elective surgery or adjuvant chemotherapy for cancer patients with low risk of progression should be considered on a case‐by‐case basis. Minimizing outpatient visits can help to mitigate exposure and possible further transmission. Telemedicine may be used to support patients to minimize number of visits and risk of exposure. More research is needed to better understand SARS‐CoV‐2 virology and epidemiology.
|Oncologist||2020||LitCov and CORD-19|
|27||Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding |
Summary Background In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. Methods We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. Findings The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. Interpretation 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. Funding National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.
|Lancet||2020||LitCov and CORD-19|
|28||A major outbreak of severe acute respiratory syndrome in Hong Kong |
|N Engl J Med||2003||CORD-19|
|29||Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study |
BACKGROUND: An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in December, 2019, in Wuhan, China. Information about critically ill patients with SARS-CoV-2 infection is scarce. We aimed to describe the clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia. METHODS: In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between survivors and non-survivors. The primary outcome was 28-day mortality, as of Feb 9, 2020. Secondary outcomes included incidence of SARS-CoV-2-related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation. FINDINGS: Of 710 patients with SARS-CoV-2 pneumonia, 52 critically ill adult patients were included. The mean age of the 52 patients was 59·7 (SD 13·3) years, 35 (67%) were men, 21 (40%) had chronic illness, 51 (98%) had fever. 32 (61·5%) patients had died at 28 days, and the median duration from admission to the intensive care unit (ICU) to death was 7 (IQR 3–11) days for non-survivors. Compared with survivors, non-survivors were older (64·6 years [11·2] vs 51·9 years [12·9]), more likely to develop ARDS (26 [81%] patients vs 9 [45%] patients), and more likely to receive mechanical ventilation (30 [94%] patients vs 7 [35%] patients), either invasively or non-invasively. Most patients had organ function damage, including 35 (67%) with ARDS, 15 (29%) with acute kidney injury, 12 (23%) with cardiac injury, 15 (29%) with liver dysfunction, and one (2%) with pneumothorax. 37 (71%) patients required mechanical ventilation. Hospital-acquired infection occurred in seven (13·5%) patients. INTERPRETATION: The mortality of critically ill patients with SARS-CoV-2 pneumonia is considerable. The survival time of the non-survivors is likely to be within 1–2 weeks after ICU admission. Older patients (>65 years) with comorbidities and ARDS are at increased risk of death. The severity of SARS-CoV-2 pneumonia poses great strain on critical care resources in hospitals, especially if they are not adequately staffed or resourced. FUNDING: None.
|Lancet Respir Med||2020||LitCov and CORD-19|
|30||The psychological impact of quarantine and how to reduce it: rapid review of the evidence |
Summary The December, 2019 coronavirus disease outbreak has seen many countries ask people who have potentially come into contact with the infection to isolate themselves at home or in a dedicated quarantine facility. Decisions on how to apply quarantine should be based on the best available evidence. We did a Review of the psychological impact of quarantine using three electronic databases. Of 3166 papers found, 24 are included in this Review. Most reviewed studies reported negative psychological effects including post-traumatic stress symptoms, confusion, and anger. Stressors included longer quarantine duration, infection fears, frustration, boredom, inadequate supplies, inadequate information, financial loss, and stigma. Some researchers have suggested long-lasting effects. In situations where quarantine is deemed necessary, officials should quarantine individuals for no longer than required, provide clear rationale for quarantine and information about protocols, and ensure sufficient supplies are provided. Appeals to altruism by reminding the public about the benefits of quarantine to wider society can be favourable.
|Lancet||2020||LitCov and CORD-19|
|31||COVID-19: consider cytokine storm syndromes and immunosuppression||Lancet||2020||LitCov and CORD-19|
|32||Presenting Characteristics, Comorbidities and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area |
|JAMA||2020||LitCov and CORD-19|
|33||The origin, transmission and clinical therapies on COVID-19 outbreak-an update on the status |
An acute respiratory disease, caused by a novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV), the coronavirus disease 2019 (COVID-19) has spread throughout China and received worldwide attention. On 30 January 2020, World Health Organization (WHO) officially declared the COVID-19 epidemic as a public health emergency of international concern. The emergence of SARS-CoV-2, since the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, marked the third introduction of a highly pathogenic and large-scale epidemic coronavirus into the human population in the twenty-first century. As of 1 March 2020, a total of 87,137 confirmed cases globally, 79,968 confirmed in China and 7169 outside of China, with 2977 deaths (3.4%) had been reported by WHO. Meanwhile, several independent research groups have identified that SARS-CoV-2 belongs to β-coronavirus, with highly identical genome to bat coronavirus, pointing to bat as the natural host. The novel coronavirus uses the same receptor, angiotensin-converting enzyme 2 (ACE2) as that for SARS-CoV, and mainly spreads through the respiratory tract. Importantly, increasingly evidence showed sustained human-to-human transmission, along with many exported cases across the globe. The clinical symptoms of COVID-19 patients include fever, cough, fatigue and a small population of patients appeared gastrointestinal infection symptoms. The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. Currently, there are few specific antiviral strategies, but several potent candidates of antivirals and repurposed drugs are under urgent investigation. In this review, we summarized the latest research progress of the epidemiology, pathogenesis, and clinical characteristics of COVID-19, and discussed the current treatment and scientific advancements to combat the epidemic novel coronavirus.
|Mil Med Res||2020||LitCov and CORD-19|
|34||A SARS-CoV-2 Surveillance System in Sub-Saharan Africa: Modeling Study for Persistence and Transmission to Inform Policy |
BACKGROUND: Since the novel coronavirus emerged in late 2019, the scientific and public health community around the world have sought to better understand, surveil, treat, and prevent the disease, COVID-19. In sub-Saharan Africa (SSA), many countries responded aggressively and decisively with lockdown measures and border closures. Such actions may have helped prevent large outbreaks throughout much of the region, though there is substantial variation in caseloads and mortality between nations. Additionally, the health system infrastructure remains a concern throughout much of SSA, and the lockdown measures threaten to increase poverty and food insecurity for the subcontinent’s poorest residents. The lack of sufficient testing, asymptomatic infections, and poor reporting practices in many countries limit our understanding of the virus’s impact, creating a need for better and more accurate surveillance metrics that account for underreporting and data contamination. OBJECTIVE: The goal of this study is to improve infectious disease surveillance by complementing standardized metrics with new and decomposable surveillance metrics of COVID-19 that overcome data limitations and contamination inherent in public health surveillance systems. In addition to prevalence of observed daily and cumulative testing, testing positivity rates, morbidity, and mortality, we derived COVID-19 transmission in terms of speed, acceleration or deceleration, change in acceleration or deceleration (jerk), and 7-day transmission rate persistence, which explains where and how rapidly COVID-19 is transmitting and quantifies shifts in the rate of acceleration or deceleration to inform policies to mitigate and prevent COVID-19 and food insecurity in SSA. METHODS: We extracted 60 days of COVID-19 data from public health registries and employed an empirical difference equation to measure daily case numbers in 47 sub-Saharan countries as a function of the prior number of cases, the level of testing, and weekly shift variables based on a dynamic panel model that was estimated using the generalized method of moments approach by implementing the Arellano-Bond estimator in R. RESULTS: Kenya, Ghana, Nigeria, Ethiopia, and South Africa have the most observed cases of COVID-19, and the Seychelles, Eritrea, Mauritius, Comoros, and Burundi have the fewest. In contrast, the speed, acceleration, jerk, and 7-day persistence indicate rates of COVID-19 transmissions differ from observed cases. In September 2020, Cape Verde, Namibia, Eswatini, and South Africa had the highest speed of COVID-19 transmissions at 13.1, 7.1, 3.6, and 3 infections per 100,0000, respectively; Zimbabwe had an acceleration rate of transmission, while Zambia had the largest rate of deceleration this week compared to last week, referred to as a jerk. Finally, the 7-day persistence rate indicates the number of cases on September 15, 2020, which are a function of new infections from September 8, 2020, decreased in South Africa from 216.7 to 173.2 and Ethiopia from 136.7 to 106.3 per 100,000. The statistical approach was validated based on the regression results; they determined recent changes in the pattern of infection, and during the weeks of September 1-8 and September 9-15, there were substantial country differences in the evolution of the SSA pandemic. This change represents a decrease in the transmission model R value for that week and is consistent with a de-escalation in the pandemic for the sub-Saharan African continent in general. CONCLUSIONS: Standard surveillance metrics such as daily observed new COVID-19 cases or deaths are necessary but insufficient to mitigate and prevent COVID-19 transmission. Public health leaders also need to know where COVID-19 transmission rates are accelerating or decelerating, whether those rates increase or decrease over short time frames because the pandemic can quickly escalate, and how many cases today are a function of new infections 7 days ago. Even though SSA is home to some of the poorest countries in the world, development and population size are not necessarily predictive of COVID-19 transmission, meaning higher income countries like the United States can learn from African countries on how best to implement mitigation and prevention efforts. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/21955
|J Med Internet Res||2020||LitCov and CORD-19|
|35||Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China |
|36||Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study |
BACKGROUND: We investigated the temporal progression of the clinical, radiological, and virological changes in a community outbreak of severe acute respiratory syndrome (SARS). METHODS: We followed up 75 patients for 3 weeks managed with a standard treatment protocol of ribavirin and corticosteroids, and assessed the pattern of clinical disease, viral load, risk factors for poor clinical outcome, and the usefulness of virological diagnostic methods. FINDINGS: Fever and pneumonia initially improved but 64 (85%) patients developed recurrent fever after a mean of 8.9 (SD 3.1) days, 55 (73%) had watery diarrhoea after 7.5 (2.3) days, 60 (80%) had radiological worsening after 7.4 (2.2) days, and respiratory symptoms worsened in 34 (45%) after 8.6 (3.0) days. In 34 (45%) patients, improvement of initial pulmonary lesions was associated with appearance of new radiological lesions at other sites. Nine (12%) patients developed spontaneous pneumomediastinum and 15 (20%) developed acute respiratory distress syndrome (ARDS) in week 3. Quantitative reverse-transcriptase (RT) PCR of nasopharyngeal aspirates in 14 patients (four with ARDS) showed peak viral load at day 10, and at day 15 a load lower than at admission. Age and chronic hepatitis B virus infection treated with lamivudine were independent significant risk factors for progression to ARDS (p=0.001). SARS-associated coronavirus in faeces was seen on RT-PCR in 65 (97%) of 67 patients at day 14. The mean time to seroconversion was 20 days. INTERPRETATION: The consistent clinical progression, shifting radiological infiltrates, and an inverted V viral-load profile suggest that worsening in week 2 is unrelated to uncontrolled viral replication but may be related to immunopathological damage. Published online May 9, 2003 http://image.thelancet.com/extras/03art4432web.pdf
|37||Global trends in emerging infectious diseases |
Emerging infectious diseases (EIDs) are a significant burden on global economies and public health(1–3). Their emergence is thought to be driven largely by socio-economic, environmental and ecological factors(1–9), but no comparative study has explicitly analysed these linkages to understand global temporal and spatial patterns of EIDs. Here we analyse a database of 335 EID ‘events’ (origins of EIDs) between 1940 and 2004, and demonstrate non-random global patterns. EID events have risen significantly over time after controlling for reporting bias, with their peak incidence (in the 1980s) concomitant with the HIV pandemic. EID events are dominated by zoonoses (60.3% of EIDs): the majority of these (71.8%) originate in wildlife (for example, severe acute respiratory virus, Ebola virus), and are increasing significantly over time. We find that 54.3% of EID events are caused by bacteria or rickettsia, reflecting a large number of drug-resistant microbes in our database. Our results confirm that EID origins are significantly correlated with socio-economic, environmental and ecological factors, and provide a basis for identifying regions where new EIDs are most likely to originate (emerging disease ‘hotspots’). They also reveal a substantial risk of wildlife zoonotic and vector-borne EIDs originating at lower latitudes where reporting effort is low. We conclude that global resources to counter disease emergence are poorly allocated, with the majority of the scientific and surveillance effort focused on countries from where the next important EID is least likely to originate.
|38||Impact of self-imposed prevention measures and short-term government-imposed social distancing on mitigating and delaying a COVID-19 epidemic: A modelling study |
BACKGROUND: The coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to nearly every country in the world since it first emerged in China in December 2019. Many countries have implemented social distancing as a measure to “flatten the curve” of the ongoing epidemics. Evaluation of the impact of government-imposed social distancing and of other measures to control further spread of COVID-19 is urgent, especially because of the large societal and economic impact of the former. The aim of this study was to compare the individual and combined effectiveness of self-imposed prevention measures and of short-term government-imposed social distancing in mitigating, delaying, or preventing a COVID-19 epidemic. METHODS AND FINDINGS: We developed a deterministic compartmental transmission model of SARS-CoV-2 in a population stratified by disease status (susceptible, exposed, infectious with mild or severe disease, diagnosed, and recovered) and disease awareness status (aware and unaware) due to the spread of COVID-19. Self-imposed measures were assumed to be taken by disease-aware individuals and included handwashing, mask-wearing, and social distancing. Government-imposed social distancing reduced the contact rate of individuals irrespective of their disease or awareness status. The model was parameterized using current best estimates of key epidemiological parameters from COVID-19 clinical studies. The model outcomes included the peak number of diagnoses, attack rate, and time until the peak number of diagnoses. For fast awareness spread in the population, self-imposed measures can significantly reduce the attack rate and diminish and postpone the peak number of diagnoses. We estimate that a large epidemic can be prevented if the efficacy of these measures exceeds 50%. For slow awareness spread, self-imposed measures reduce the peak number of diagnoses and attack rate but do not affect the timing of the peak. Early implementation of short-term government-imposed social distancing alone is estimated to delay (by at most 7 months for a 3-month intervention) but not to reduce the peak. The delay can be even longer and the height of the peak can be additionally reduced if this intervention is combined with self-imposed measures that are continued after government-imposed social distancing has been lifted. Our analyses are limited in that they do not account for stochasticity, demographics, heterogeneities in contact patterns or mixing, spatial effects, imperfect isolation of individuals with severe disease, and reinfection with COVID-19. CONCLUSIONS: Our results suggest that information dissemination about COVID-19, which causes individual adoption of handwashing, mask-wearing, and social distancing, can be an effective strategy to mitigate and delay the epidemic. Early initiated short-term government-imposed social distancing can buy time for healthcare systems to prepare for an increasing COVID-19 burden. We stress the importance of disease awareness in controlling the ongoing epidemic and recommend that, in addition to policies on social distancing, governments and public health institutions mobilize people to adopt self-imposed measures with proven efficacy in order to successfully tackle COVID-19.
|PLoS Med||2020||LitCov and CORD-19|
|39||Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1||N Engl J Med||2020||LitCov and CORD-19|
|40||Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia |
|N Engl J Med||2012||CORD-19|
|41||A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster |
BACKGROUND: An ongoing outbreak of pneumonia associated with a novel coronavirus was reported in Wuhan city, Hubei province, China. Affected patients were geographically linked with a local wet market as a potential source. No data on person-to-person or nosocomial transmission have been published to date. METHODS: In this study, we report the epidemiological, clinical, laboratory, radiological, and microbiological findings of five patients in a family cluster who presented with unexplained pneumonia after returning to Shenzhen, Guangdong province, China, after a visit to Wuhan, and an additional family member who did not travel to Wuhan. Phylogenetic analysis of genetic sequences from these patients were done. FINDINGS: From Jan 10, 2020, we enrolled a family of six patients who travelled to Wuhan from Shenzhen between Dec 29, 2019 and Jan 4, 2020. Of six family members who travelled to Wuhan, five were identified as infected with the novel coronavirus. Additionally, one family member, who did not travel to Wuhan, became infected with the virus after several days of contact with four of the family members. None of the family members had contacts with Wuhan markets or animals, although two had visited a Wuhan hospital. Five family members (aged 36–66 years) presented with fever, upper or lower respiratory tract symptoms, or diarrhoea, or a combination of these 3–6 days after exposure. They presented to our hospital (The University of Hong Kong-Shenzhen Hospital, Shenzhen) 6–10 days after symptom onset. They and one asymptomatic child (aged 10 years) had radiological ground-glass lung opacities. Older patients (aged >60 years) had more systemic symptoms, extensive radiological ground-glass lung changes, lymphopenia, thrombocytopenia, and increased C-reactive protein and lactate dehydrogenase levels. The nasopharyngeal or throat swabs of these six patients were negative for known respiratory microbes by point-of-care multiplex RT-PCR, but five patients (four adults and the child) were RT-PCR positive for genes encoding the internal RNA-dependent RNA polymerase and surface Spike protein of this novel coronavirus, which were confirmed by Sanger sequencing. Phylogenetic analysis of these five patients' RT-PCR amplicons and two full genomes by next-generation sequencing showed that this is a novel coronavirus, which is closest to the bat severe acute respiatory syndrome (SARS)-related coronaviruses found in Chinese horseshoe bats. INTERPRETATION: Our findings are consistent with person-to-person transmission of this novel coronavirus in hospital and family settings, and the reports of infected travellers in other geographical regions. FUNDING: The Shaw Foundation Hong Kong, Michael Seak-Kan Tong, Respiratory Viral Research Foundation Limited, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund Limited, Marina Man-Wai Lee, the Hong Kong Hainan Commercial Association South China Microbiology Research Fund, Sanming Project of Medicine (Shenzhen), and High Level-Hospital Program (Guangdong Health Commission).
|Lancet||2020||LitCov and CORD-19|
|42||Factors Associated With Mental Health Disorders Among University Students in France Confined During the COVID-19 Pandemic |
IMPORTANCE: The coronavirus disease 2019 (COVID-19) pandemic and quarantine measures have raised concerns regarding their psychological effects on populations. Among the general population, university students appear to be particularly susceptible to experiencing mental health problems. OBJECTIVES: To measure the prevalence of self-reported mental health symptoms, to identify associated factors, and to assess care seeking among university students who experienced the COVID-19 quarantine in France. DESIGN, SETTING, AND PARTICIPANTS: This survey study collected data from April 17 to May 4, 2020, from 69 054 students living in France during the COVID-19 quarantine. All French universities were asked to send an email to their students asking them to complete an online questionnaire. The targeted population was approximately 1 600 000 students. EXPOSURE: Living in France during the COVID-19 quarantine. MAIN OUTCOMES AND MEASURES: The rates of self-reported suicidal thoughts, severe distress, stress, anxiety, and depression were assessed using the 22-item Impact of Events Scale–Revised, the 10-item Perceived Stress Scale, the 20-item State-Trait Anxiety Inventory (State subscale), and the 13-item Beck Depression Inventory, respectively. Covariates were sociodemographic characteristics, precariousness indicators (ie, loss of income or poor quality housing), health-related data, information on the social environment, and media consumption. Data pertaining to care seeking were also collected. Multivariable logistic regression analyses were performed to identify risk factors. RESULTS: A total of 69 054 students completed the survey (response rate, 4.3%). The median (interquartile range) age was 20 (18-22) years. The sample was mainly composed of women (50 251 [72.8%]) and first-year students (32 424 [47.0%]). The prevalence of suicidal thoughts, severe distress, high level of perceived stress, severe depression, and high level of anxiety were 11.4% (7891 students), 22.4% (15 463 students), 24.7% (17 093 students), 16.1% (11 133 students), and 27.5% (18 970 students), respectively, with 29 564 students (42.8%) reporting at least 1 outcome, among whom 3675 (12.4%) reported seeing a health professional. Among risk factors identified, reporting at least 1 mental health outcome was associated with female gender (odds ratio [OR], 2.10; 95% CI, 2.02-2.19; P < .001) or nonbinary gender (OR, 3.57; 95% CI, 2.99-4.27; P < .001), precariousness (loss of income: OR, 1.28; 95% CI, 1.22-1.33; P < .001; low-quality housing: OR, 2.30; 95% CI, 2.06-2.57; P < .001), history of psychiatric follow-up (OR, 3.28; 95% CI, 3.09-3.48; P < .001), symptoms compatible with COVID-19 (OR, 1.55; 95% CI, 1.49-1.61; P < .001), social isolation (weak sense of integration: OR, 3.63; 95% CI, 3.35-3.92; P < .001; low quality of social relations: OR, 2.62; 95% CI, 2.49-2.75; P < .001), and low quality of the information received (OR, 1.56; 95% CI, 1.49-1.64; P < .001). CONCLUSIONS AND RELEVANCE: The results of this survey study suggest a high prevalence of mental health issues among students who experienced quarantine, underlining the need to reinforce prevention, surveillance, and access to care.
|JAMA Netw Open||2020||LitCov and CORD-19|
|43||Identification of severe acute respiratory syndrome in Canada |
|N Engl J Med||2003||CORD-19|
|44||Digital Approaches to Remote Pediatric Healthcare Delivery During the COVID-19 Pandemic: Existing Evidence and a Call for Further Research |
The global spread of the coronavirus disease (COVID-19) outbreak poses a public health threat and has affected people worldwide in various unprecedented ways, both personally and professionally. There is no question that the current global COVID-19 crisis, now more than ever, is underscoring the importance of leveraging digital approaches to optimize pediatric health care delivery in the era of this pandemic. In this perspective piece, we highlight some of the available digital approaches that have been and can continue to be used to streamline remote pediatric patient care in the era of the COVID-19 pandemic, including but not limited to telemedicine. JMIR Pediatrics and Parenting is currently publishing a COVID-19 special theme issue in which investigators can share their interim and final research data related to digital approaches to remote pediatric health care delivery in different settings. The COVID-19 pandemic has rapidly transformed health care systems worldwide, with significant variations and innovations in adaptation. There has been rapid expansion of the leveraging and optimization of digital approaches to health care delivery, particularly integrated telemedicine and virtual health. Digital approaches have played and will play major roles as invaluable and reliable resources to overcome restrictions and challenges imposed during the COVID-19 pandemic and to increase access to effective, accessible, and consumer-friendly care for more patients and families. However, a number of challenges remain to be addressed, and further research is needed. Optimizing digital approaches to health care delivery and integrating them into the public health response will be an ongoing process during the current COVID-19 outbreak and during other possible future pandemics. Regulatory changes are essential to support the safe and wide adoption of these approaches. Involving all relevant stakeholders in addressing current and future challenges as well as logistical, technological, and financial barriers will be key for success. Future studies should consider evaluating the following research areas related to telemedicine and other digital approaches: cost-effectiveness and return on investment; impact on quality of care; balance in use and number of visits needed for the management of both acute illness and chronic health conditions; system readiness for further adoption in other settings, such as inpatient services, subspecialist consultations, and rural areas; ongoing user-centered evaluations, with feedback from patients, families, and health care providers; strategies to optimize health equity and address disparities in access to care related to race and ethnicity, socioeconomic status, immigration status, and rural communities; privacy and security concerns for protected health information with Health Insurance Portability and Accountability Act (HIPAA)–secured programs; confidentiality issues for some specific populations, especially adolescents and those in need of mental health services; early detection of exposure to violence and child neglect; and integration of training into undergraduate and graduate medical education and subspecialty fellowships. Addressing these research areas is essential to understanding the benefits, sustainability, safety, and optimization strategies of telemedicine and other digital approaches as key parts of modern health care delivery. These efforts will inform long-term adoption of these approaches with expanded dissemination and implementation efforts.
|JMIR Pediatr Parent||2020||LitCov and CORD-19|
|45||Inappropriate risk perception for SARS-CoV-2 infection among Italian HCWs in the eve of COVID-19 pandemic |
Sir, Italy has been recently involved in the outbreak of severe interstitial pneumonia associated with the previously unknown Coronavirus SARS-CoV-2 (1,2). Even before the notification of the first autochthonous cases, the SARS-CoV-2 associated syndrome (COVID-19) had raised an intense attention in the public opinion (3), with a counterproductive over-abundance of mixed quality information. As even Italian healthcare workers (HCWs) were not spared by subsequent misunderstandings and knowledge gaps during the previous influenza pandemic of 2009 (4), we performed a web-based survey (Google® Modules), specifically aimed to characterize knowledge status and risk perceptions in a sample from participating to 6 Facebook discussion groups (181,684 total unique members at the time of the study). The questionnaire was made available between February 1st and 7th, 2020, i.e. around 2 weeks before the first COVID-19 was officially diagnosed in Italian residents. Overall, the sampled population included 2106 respondents (Table 1), and 39.3% were HCWs. Even though HCWs were more likely to exhibit a better understanding of SARS-CoV-2/COVID-19 related issues (aOR 2.195, 95%CI 1.809 to 2.664), they were not exempt for misunderstandings, particularly on actual incidence and lethality of COVID-19. Interestingly, most of respondents were aware of the main clinical features of COVID-19, with HCWs more frequently acknowledging that the COVID-19 may run pauci- or even asymptomatic (86.3% vs. 79.1%), resembling an Influenza-Like Illness (i.e. fever, cough, headache, etc.), with a potential latency up to 14 days (85·9% vs· 80·3%), eventually spreading by droplets (98.5% vs. 92.7%) rather through running water (92.3% vs· 79.8%), or blood/body fluids (88.0% vs. 70.4%). Retrospectively, the assessment of preventive measures and risk perception appears somewhat worrisome. For instance, while HCWs were more likely to acknowledge as an appropriate preventive measure wearing a filtering mask (i.e. N95/FFP2/3 mask; aOR 2.296, 95%CI 1.507 to 3.946), around ¼ of HCWs failed to recognize the importance of such personal protective equipment, while 7.4% felt as appropriate the wearing of a surgical mask. Moreover, not only COVID-19 was appropriately acknowledged as a severe disease by only 62.0% of respondents, with no differences between HCWs and non-HCWs, but an even smaller share (i.e. 8.0%) reported any concern for being infected by SARS-CoV-2 in Italy. In fact, at the time of the survey SARS-CoV-2 was more properly associated with international travelers (26.7%). Our results are therefore of certain interests for several reasons. First at all, early epidemiological reports on the Italian cases of COVID-19 hint towards some failures in the initial management of incident cases (5-6). In fact, in our survey a large share of respondents substantially overlooked the risk to interact with SARS-CoV-2 positive subjects, that was otherwise perceived as a not-so-severe disease (i.e. nothing more than a seasonal flu, as often described in some social media) (7). Moreover, around a 1/3 of HCWs participating to the study presumptively did not use proper personal protective equipment for the airways interacting with possible COVID-19 cases, either underestimating the infection risk or being unable to recognize early symptoms. Actually, the base of evidence shared by participants at the time of the study substantially ignored that COVID-19 may be characterized by dermatologic and gastro-intestinal symptoms (8-9). As most of infections may be actually pauci- or asymptomatic, such early exposure in the healthcare settings may have contributed to the quick spreading of SARS-CoV-2 epidemic in Northern Italy. Therefore, despite the intrinsic limits of a convenience sampling, web-based survey (10), our study stresses the importance to improve the overall quality of information on COVID-19 conveyed not only in HCWs, but also in the general population. Moreover, our data may contribute to clarify the early stages of SARS-CoV-2 pandemic in Italy.
|Acta Biomed||2020||LitCov and CORD-19|
|46||Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area |
|47||SARS-CoV-2 and coronavirus disease-2019: The epidemic and the challenges |
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; previously provisionally named 2019 novel coronavirus or 2019-nCoV) disease (COVID-19) in China at the end of 2019 has caused a large global outbreak and is a major public health issue. As of 11 February 2020, data from the World Health Organization (WHO) have shown that more than 43 000 confirmed cases have been identified in 28 countries/regions, with >99% of cases being detected in China. On 30 January 2020, the WHO declared COVID-19 as the sixth public health emergency of international concern. SARS-CoV-2 is closely related to two bat-derived severe acute respiratory syndrome-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21. It is spread by human-to-human transmission via droplets or direct contact, and infection has been estimated to have mean incubation period of 6.4 days and a basic reproduction number of 2.24–3.58. Among patients with pneumonia caused by SARS-CoV-2 (novel coronavirus pneumonia or Wuhan pneumonia), fever was the most common symptom, followed by cough. Bilateral lung involvement with ground-glass opacity was the most common finding from computed tomography images of the chest. The one case of SARS-CoV-2 pneumonia in the USA is responding well to remdesivir, which is now undergoing a clinical trial in China. Currently, controlling infection to prevent the spread of SARS-CoV-2 is the primary intervention being used. However, public health authorities should keep monitoring the situation closely, as the more we can learn about this novel virus and its associated outbreak, the better we can respond.
|Int J Antimicrob Agents||2020||LitCov and CORD-19|
|48||Health workers' perceptions and experiences of using mHealth technologies to deliver primary healthcare services: a qualitative evidence synthesis |
|Cochrane Database Syst Rev||2020||CORD-19|
|49||Why COVID-19 Transmission Is More Efficient and Aggressive Than Viral Transmission in Previous Coronavirus Epidemics? |
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing a pandemic of coronavirus disease 2019 (COVID-19). The worldwide transmission of COVID-19 from human to human is spreading like wildfire, affecting almost every country in the world. In the past 100 years, the globe did not face a microbial pandemic similar in scale to COVID-19. Taken together, both previous outbreaks of other members of the coronavirus family (severe acute respiratory syndrome (SARS-CoV) and middle east respiratory syndrome (MERS-CoV)) did not produce even 1% of the global harm already inflicted by COVID-19. There are also four other CoVs capable of infecting humans (HCoVs), which circulate continuously in the human population, but their phenotypes are generally mild, and these HCoVs received relatively little attention. These dramatic differences between infection with HCoVs, SARS-CoV, MERS-CoV, and SARS-CoV-2 raise many questions, such as: Why is COVID-19 transmitted so quickly? Is it due to some specific features of the viral structure? Are there some specific human (host) factors? Are there some environmental factors? The aim of this review is to collect and concisely summarize the possible and logical answers to these questions.
|Biomolecules||2020||LitCov and CORD-19|
|50||Repurposing of chlorpromazine in COVID-19 treatment: the reCoVery study |
Abstract OBJECTIVES: The ongoing COVID-19 pandemic comprises a total of more than 2 350 000 cases and 160 000 deaths. The interest in anti-coronavirus drug development has been limited so far and effective methods to prevent or treat coronavirus infections in humans are still lacking. Urgent action is needed to fight this fatal coronavirus infection by reducing the number of infected people along with the infection contagiousness and severity. Since the beginning of the COVID-19 outbreak several weeks ago, we observe in GHU PARIS Psychiatrie & Neurosciences (Sainte-Anne hospital, Paris, France) a lower prevalence of symptomatic and severe forms of COVID-19 infections in psychiatric patients (∼4 %) compared to health care professionals (∼14 %). Similar observations have been noted in other psychiatric units in France and abroad. Our hypothesis is that psychiatric patients could be protected from the severe form of COVID-19 by their psychotropic treatments. Chlorpromazine (CPZ) is a phenothiazine derivative widely used in clinical routine in the treatment of acute and chronic psychoses. This first antipsychotic medication has been discovered in 1952 by Jean Delay and Pierre Deniker at Sainte-Anne hospital. In addition to its antipsychotic effects, several in vitro studies have also demonstrated a CPZ antiviral activity via the inhibition of clathrin-mediated endocytosis. Recently, independent studies revealed that CPZ is an anti-MERS-CoV and an anti-SARS-CoV-1 drug. In comparison to other antiviral drugs, the main advantages of CPZ lie in its biodistribution: (i) preclinical and clinical studies have reported a high CPZ concentration in the lungs (20--200 times higher than in plasma), which is critical because of the respiratory tropism of SARS-CoV-2; (ii) CPZ is highly concentrated in saliva (20-60 times higher than in plasma) and could therefore reduce the contagiousness of COVID-19; (iii) CPZ can cross the blood-brain barrier and could therefore prevent the neurological forms of COVID-19. METHODS: In this context, we will test the hypothesis that CPZ could decrease the unfavorable evolution of COVID-19 infection in oxygen-requiring patients without the need for intensive care, but also reduce the contagiousness of SARS-CoV-2. At this end, we designed a pilot, phase III, multicenter, single blind, randomized controlled therapeutic trial. Efficacy of CPZ will be assessed according to clinical, biological and radiological criteria. The main objective is to demonstrate a shorter Time To Response (TTR) to treatment in the CPZ + standard-of-care (CPZ + SOC) group, compared to the SOC group. Response to treatment is defined by a reduction of at least one level of severity on the WHO-Ordinal Scale for Clinical Improvement (WHO-OSCI). The secondary objectives are to demonstrate in the CPZ + SOC group, compared to the SOC group: A) superior clinical improvement; B) a greater decrease in the biological markers of viral attack by SARS-CoV-2 (PCR, viral load); C) a greater decrease in inflammatory markers (e.g. CRP and lymphopenia); D) a greater decrease in parenchymal involvement (chest CT) on the seventh day post-randomization; E) to define the optimal dosage of CPZ and its tolerance; F) to evaluate the biological parameters of response to treatment, in particular the involvement of inflammatory cytokines. Patient recruitment along with the main and secondary objectives are in line with WHO 2020 COVID-19 guidelines. CONCLUSION: This repositioning of CPZ as anti-SARS-CoV-2 activity offers an alternative and rapid strategy to alleviate the virus propagation and the infection severity and lethality. This CPZ repositioning strategy also avoids numerous developmental and experimental steps, can save precious time to rapidly establish an anti-COVID-19 therapy with well-known, limited and easy to manage side effects. Indeed, CPZ is an FDA-approved drug with an excellent tolerance profile, prescribed for around 70 years, in psychiatry but also in clinical routine in nausea and vomiting of pregnancy, in advanced cancer and also to treat headaches in various neurological conditions. The broad spectrum of CPZ treatment - including antipsychotic, anxiolytic, antiemetic, antiviral, immunomodulatory effects along with inhibition of clathrin-mediated endocytosis and modulation of blood-brain barrier - is in line with the historical French commercial name for CPZ, i.e. LARGACTIL, chosen as a reference to its 'LARGe ACTion' properties. The discovery of those CPZ properties, as for many other molecules in psychiatry, is both the result of serendipity and careful clinical observations. Using this approach, the field of mental illness could provide innovative therapeutic approaches to fight SARS-CoV-2.
|Encephale||2020||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 2022-09-06)
(3) Currently tweets of June 23rd to June 29th 2022 have been considered.