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    This special COVID-19 Pandemic research topic is intended to be a resource where reputable scientific papers, reports, articles and websites are listed. New material will be continually added, so please check back frequently. Material in Green provides basic information and advice. Non-green material may contain detailed medical and scientific information which some readers may wish to avoid. Click on the title of a paper you are interested in to go straight to the full paper. If you know about other material that might be suitable, please reply to this topic with details or alternatively private message me. Q&A on coronaviruses (COVID-19) A Q&A by The World Health Organisation WHO). They are continuously monitoring and responding to this outbreak so this Q&A will be updated as more is known about COVID-19, how it spreads and how it is affecting people worldwide, so check back regularly. NHS advice about the coronavirus (COVID-19) NHS website containing information and advice. Stay at home: guidance for people with confirmed or possible coronavirus (COVID-19) infection Published 12 March 2020 by Public Health England. Stay at home advice (NHS) NHS website Guidance on shielding and protecting people defined on medical grounds as extremely vulnerable from COVID-19 Published 21 March 2020 by Public Health England Looking after your mental health during the Coronavirus outbreak Published 11 March 2020 by The Mental Health Foundation. COVID-19 Virus Infection and Pregnancy 2020 publication by the Royal College of Obstetricians and Gynaecologists. Contains information for pregnant women and their families. Covid-19: How long does the coronavirus last on surfaces? Published 17 Mar 2020 by BBC World. No abstract, but this is the intro: "We can pick up the Covid-19 by touching surfaces contaminated with the new coronavirus, but it is only just becoming clear how long the virus can survive outside the human body." Note: the study referred to by the BBC can be found below - Aerosol and Surface Stability. Guidance on the closure of all non-essential businesses and premises as part of further social distancing measures First published 23 March 2020 by HM Government. Claim a grant through the coronavirus (COVID-19) Self-employment Income Support Scheme Published 26 March 2020 by HM Revenue & Customs Testing the Efficacy of Homemade Masks: Would They Protect in an Influenza Pandemic? Published 2013 and written by Anna Davies University of Cambridge and Katy-Anne Thompson, Public Health England. Abstract: This study examined homemade masks as an alternative to commercial face masks. Several household materials were evaluated for the capacity to block bacterial and viral aerosols. Twenty-one healthy volunteers made their own face masks from cotton t-shirts; the masks were then tested for fit. The number of microorganisms isolated from coughs of healthy volunteers wearing their homemade mask, a surgical mask, or no mask was compared using several air-sampling techniques. The median-fit factor of the homemade masks was one-half that of the surgical masks. Both masks significantly reduced the number of microorganisms expelled by volunteers, although the surgical mask was 3 times more effective in blocking transmission than the homemade mask. Our findings suggest that a homemade mask should only be considered as a last resort to prevent droplet transmission from infected individuals, but it would be better than no protection. Global research on coronavirus disease (COVID-19) WHO is gathering the latest scientific findings and knowledge on COVID-19 and compiling it in a database. They update the database daily and you can download it via this link. COVID-19 Resource Centre - The Lancet To assist health workers and researchers working under challenging conditions to bring this outbreak to a close, The Lancet has created a Coronavirus Resource Centre. This resource brings together new 2019 novel coronavirus disease (COVID-19) content from across The Lancet journals as it is published. All of the COVID-19 content is free to access. The perfect virus: two gene tweaks that turned COVID-19 into a killer Published 29 March 2020. Article by Liam Mannix, The Age and Sydney Morning Herald's science reporter. No abstract but this is a fascinating article about the likely origins and emergence of the COVID-19 virus. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1 Published 17 Mar 2020 by the New England Journal of Medicine. Abstract: A novel human coronavirus that is now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (formerly called HCoV-19) emerged in Wuhan, China, in late 2019 and is now causing a pandemic.1 We analyzed the aerosol and surface stability of SARS-CoV-2 and compared it with SARS-CoV-1, the most closely related human coronavirus. (See also the BBC article above in Green: Covid-19: How long does the coronavirus last on surfaces?) Symptom progression of COVID-19 Published 11 March 2020 by Imperial College London. Abstract: The COVID-19 epidemic was declared a Public Health Emergency of International Concern (PHEIC) by WHO on 30th January 2020 [1]. As of 8 March 2020,over107,000 cases had been reported. Here, we use published and pre-print studies of clinical characteristics of cases in mainland China as well as case studies of individuals from Hong Kong, Japan, Singapore and South Korea to examine the proportional occurrence of symptoms and the progression of symptoms through time.We find that in mainland China, where specific symptoms or disease presentation are reported, pneumonia is the most frequently mentioned, see figure 1. We found a more varied spectrum of severity in cases outside mainland China. In Hong Kong, Japan, Singapore and South Korea, fever was the most frequently reported symptom. In this latter group, presentation with pneumonia is not reported as frequently although it is more common in individuals over 60 years old.The average time from reported onset of first symptoms to the occurrence of specific symptoms or disease presentation, such as pneumonia or the use of mechanical ventilation,varied substantially. The average time to presentation with pneumonia is 5.88 days, and may be linked to testing at hospitalisation; feveris often reported at onset (where the mean time to develop fever is0.77 days). Transmissibility of 2019-nCoV Published 25 Jan 2020 by Imperial College London Abstract: Self-sustaining human-to-human transmission of the novel coronavirus COVID-19 (previously termed 2019-nCoV) is the only plausible explanation of the scale of the outbreak in Wuhan. We estimate that, on average, each case infected 2.6 (uncertainty range: 1.5-3.5) other people up to 18th January 2020, based on an analysis combining our past estimates of the size of the outbreak in Wuhan with computational modelling of potential epidemic trajectories. This implies that control measures need to block well over 60% of transmission to be effective in controlling the outbreak. It is likely, based on the experience of SARS and MERS-CoV, that the number of secondary cases caused by a case of COVID-19 is highly variable – with many cases causing no secondary infections, and a few causing many. Whether transmission is continuing at the same rate currently depends on the effectiveness of current control measures implemented in China and the extent to which the populations of affected areas have adopted risk-reducing behaviours. In the absence of antiviral drugs or vaccines, control relies upon the prompt detection and isolation of symptomatic cases. It is unclear at the current time whether this outbreak can be contained within China; uncertainties include the severity spectrum of the disease caused by this virus and whether cases with relatively mild symptoms are able to transmit the virus efficiently. Identification and testing of potential cases need to be as extensive as is permitted by healthcare and diagnostic testing capacity – including the identification, testing and isolation of suspected cases with only mild to moderate disease (e.g. influenza-like illness), when logistically feasible. Severity of 2019-novel coronavirus (nCoV) Published 10 February 2020 by Imperial College London. Abstract: We present case fatality ratio (CFR) estimates for three strata of COVID-19 (previously termed 2019-nCoV) infections. For cases detected in Hubei, we estimate the CFR to be 18% (95% credible interval: 11%-81%). For cases detected in travellers outside mainland China, we obtain central estimates of the CFR in the range 1.2-5.6% depending on the statistical methods, with substantial uncertainty around these central values. Using estimates of underlying infection prevalence in Wuhan at the end of January derived from testing of passengers on repatriation flights to Japan and Germany, we adjusted the estimates of CFR from either the early epidemic in Hubei Province, or from cases reported outside mainland China, to obtain estimates of the overall CFR in all infections (asymptomatic or symptomatic) of approximately 1% (95% confidence interval 0.5%-4%). It is important to note that the differences in these estimates does not reflect underlying differences in disease severity between countries. CFRs seen in individual countries will vary depending on the sensitivity of different surveillance systems to detect cases of differing levels of severity and the clinical care offered to severely ill cases. All CFR estimates should be viewed cautiously at the current time as the sensitivity of surveillance of both deaths and cases in mainland China is unclear. Furthermore, all estimates rely on limited data on the typical time intervals from symptom onset to death or recovery which influences the CFR estimates. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Article published in The Lancet 11 March 2020. Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020 Published 12 March 2020. Abstract: An outbreak of coronavirus disease 2019 (COVID-19) unfolded on board a Princess Cruises’ ship called the Diamond Princess. Shortly after arriving in Yokohama, Japan, this ship had been placed under quarantine orders from 5 February 2020, after a former passenger had tested positive for the virus responsible for the disease (i.e. severe acute respiratory syndrome coronavirus 2; SARS-CoV-2), subsequent to disembarking in Hong Kong. In this study, we conducted a statistical modelling analysis to estimate the proportion of asymptomatic individuals among those who tested positive for SARS-CoV-2 on board the ship until 20 February 2020 included, along with their times of infections. The model accounted for the delay in symptom onset and also for right censoring, which can occur due to the time lag between a patient’s examination and sample collection and the development of illness. Impact of non-pharmaceutical interventions (NPIs) to reduce COVID-19 mortality and healthcare demand Published 16 March 2020 Abstract: The global impact of COVID-19 has been profound, and the public health threat it represents is the most serious seen in a respiratory virus since the 1918 H1N1 influenza pandemic.Here we present the results of epidemiological modelling which has informed policy making in the UK and other countries in recent weeks. In the absence of a COVID-19 vaccine, we assess the potential role of a number of public health measures –so-called non-pharmaceutical interventions (NPIs) –aimed at reducing contact rates in the population and thereby reducing transmission of the virus. In the results presented here, we apply a previously published micro simulation model to two countries: the UK (Great Britain specifically) and the US. We conclude that the effectiveness of any one intervention in isolation is likely to be limited, requiring multiple interventions to be combined to have a substantial impact on transmission. Report of the World Health Organisation / China Joint Mission on Coronavirus Disease 2019 (COVID-19) Published Feb 2020. No abstract. The neuroinvasive potential of SARS‐CoV2 may be at least partially responsible for the respiratory failure of COVID‐19 patients Published 20 Feb 2020. Abstract: Following the severe acute respiratory syndrome coronavirus (SARS‐CoV) and Middle East respiratory syndrome coronavirus (MERS‐CoV), another highly pathogenic coronavirus named SARS‐CoV‐2 (previously known as 2019‐nCoV) emerged in December 2019 in Wuhan, China, and rapidly spreads around the world. This virus shares highly homological sequence with SARS‐CoV, and causes acute, highly lethal pneumonia coronavirus disease 2019 (COVID‐19) with clinical symptoms similar to those reported for SARS‐CoV and MERS‐CoV. The most characteristic symptom of patients with COVID‐19 is respiratory distress, and most of the patients admitted to the intensive care could not breathe spontaneously. Additionally, some patients with COVID‐19 also showed neurologic signs, such as headache, nausea, and vomiting. Increasing evidence shows that coronaviruses are not always confined to the respiratory tract and that they may also invade the central nervous system inducing neurological diseases. The infection of SARS‐CoV has been reported in the brains from both patients and experimental animals, where the brainstem was heavily infected. Furthermore, some coronaviruses have been demonstrated able to spread via a synapse‐connected route to the medullary cardiorespiratory center from the mechanoreceptors and chemoreceptors in the lung and lower respiratory airways. In light of the high similarity between SARS‐CoV and SARS‐CoV2, it is quite likely that the potential invasion of SARS‐CoV2 is partially responsible for the acute respiratory failure of patients with COVID‐19. Awareness of this will have important guiding significance for the prevention and treatment of the SARS‐CoV‐2‐induced respiratory failure. Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia Published 13 March 2020. Abstract: A coronavirus (HCoV-19) has caused the novel coronavirus disease (COVID-19) outbreak in Wuhan, China. Preventing and reversing the cytokine storm may be the key to save the patients with severe COVID-19 pneumonia. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate whether MSC transplantation improves the outcome of 7 enrolled patients with COVID-19 pneumonia in Beijing YouAn Hospital, China, from Jan 23, 2020 to Feb 16, 2020. The clinical outcomes, as well as changes of inflammatory and immune function levels and adverse effects of 7 enrolled patients were assessed for 14 days after MSC injection. MSCs could cure or significantly improve the functional outcomes of seven patients without observed adverse effects. The pulmonary function and symptoms of these seven patients were significantly improved in 2 days after MSC transplantation. Among them, two common and one severe patient were recovered and discharged in 10 days after treatment. After treatment, the peripheral lymphocytes were increased, the C-reactive protein decreased, and the overactivated cytokine-secreting immune cells CXCR3+CD4+ T cells, CXCR3+CD8+ T cells, and CXCR3+ NK cells disappeared in 3-6 days. In addition, a group of CD14+CD11c+CD11bmid regulatory DC cell population dramatically increased. Meanwhile, the level of TNF-α was significantly decreased, while IL-10 increased in MSC treatment group compared to the placebo control group. Furthermore, the gene expression profile showed MSCs were ACE2- and TMPRSS2- which indicated MSCs are free from COVID-19 infection. Thus, the intravenous transplantation of MSCs was safe and effective for treatment in patients with COVID-19 pneumonia, especially for the patients in critically severe condition. Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV2) Published 16 March 2020. Abstract: Estimation of the prevalence and contagiousness of undocumented novel coronavirus (SARS-CoV2) infections is critical for understanding the overall prevalence and pandemic potential of this disease. Here we use observations of reported infection within China, in conjunction with mobility data, a networked dynamic metapopulation model and Bayesian inference, to infer critical epidemiological characteristics associated with SARS-CoV2, including the fraction of undocumented infections and their contagiousness. We estimate 86% of all infections were undocumented (95% CI: [82%–90%]) prior to 23 January 2020 travel restrictions. Per person, the transmission rate of undocumented infections was 55% of documented infections ([46%–62%]), yet, due to their greater numbers, undocumented infections were the infection source for 79% of documented cases. These findings explain the rapid geographic spread of SARS-CoV2 and indicate containment of this virus will be particularly challenging. Modes of transmission of virus causing COVID-19: implications for IPC precaution recommendations Published 27 March 2020 by the World Health Organisation (WHO) No abstract. The proximal origin of SARS-CoV-2 Published 17 March 2020 by Nature Medicine. Abstract: SARS-CoV-2 is the seventh coronavirus known to infect humans; SARS-CoV, MERS-CoV and SARS-CoV-2 can cause severe disease, whereas HKU1, NL63, OC43 and 229E are associated with mild symptoms6. Here we review what can be deduced about the origin of SARS-CoV-2 from comparative analysis of genomic data. We offer a perspective on the notable features of the SARS-CoV-2 genome and discuss scenarios by which they could have arisen. Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus. Can you kill coronavirus with UV light? Published 27th March 2020 by the BBC. Headline: There’s only one type of UV that can reliably inactivate Covid-19 – and it’s extremely dangerous. Impact of non-pharmaceutical interventions (NPIs) to reduce COVID-19 mortality and healthcare demand Published 16th March 2020 by Imperial College London. Summary: The global impact of COVID-19 has been profound, and the public health threat it represents is the most serious seen in a respiratory virus since the 1918 H1N1 influenza pandemic. Here we present the results of epidemiological modelling which has informed policy making in the UK and other countries in recent weeks. In the absence of a COVID-19 vaccine, we assess the potential role of a number of public health measures – so-called non-pharmaceutical interventions (NPIs) – aimed at reducing contact rates in the population and thereby reducing transmission of the virus. In the results presented here, we apply a previously published micro simulation model to two countries: the UK (Great Britain specifically) and the US. We conclude that the effectiveness of any one intervention in isolation is likely to be limited, requiring multiple interventions to be combined to have a substantial impact on transmission. Two fundamental strategies are possible: (a) mitigation, which focuses on slowing but not necessarily stopping epidemic spread – reducing peak healthcare demand while protecting those most at risk of severe disease from infection, and (b) suppression, which aims to reverse epidemic growth, reducing case numbers to low levels and maintaining that situation indefinitely. Each policy has major challenges. We find that that optimal mitigation policies (combining home isolation of suspect cases, home quarantine of those living in the same household as suspect cases, and social distancing of the elderly and others at most risk of severe disease) might reduce peak healthcare demand by 2/3 and deaths by half. However, the resulting mitigated epidemic would still likely result in hundreds of thousands of deaths and health systems (most notably intensive care units) being overwhelmed many times over. For countries able to achieve it, this leaves suppression as the preferred policy option. We show that in the UK and US context, suppression will minimally require a combination of social distancing of the entire population, home isolation of cases and household quarantine of their family members. This may need to be supplemented by school and university closures, though it should be recognised that such closures may have negative impacts on health systems due to increased absenteeism. The major challenge of suppression is that this type of intensive intervention package – or something equivalently effective at reducing transmission – will need to be maintained until a vaccine becomes available (potentially 18 months or more) – given that we predict that transmission will quickly rebound if interventions are relaxed. We show that intermittent social distancing – triggered by trends in disease surveillance – may allow interventions to be relaxed temporarily in relative short time windows, but measures will need to be reintroduced if or when case numbers rebound. Last, while experience in China and now South Korea show that suppression is possible in the short term, it remains to be seen whether it is possible long-term, and whether the social and economic costs of the interventions adopted thus far can be reduced.
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