This website is intended for healthcare professionals only.
Take a look at a selection of our recent media coverage:
30th October 2020
The approval requires that remdesivir is only used in a hospital or healthcare setting capable or providing acute care which is comparable to hospital care. This new approval does not however, include the entire population that was originally included via the emergency use authorisation (EUA) issued on 1 May 2020. In order to allow continued use in paediatric patients the EUA was amended for use only in laboratory confirmed COVID-19 cases for patients weighing 3.5 to less than 40kg less or hospitalised children under 12 years of age weighing at least 3.5kg. However, the FDA makes clear that this is NOT an approved use of the drug and that this authorisation is only temporary and could be revoked.
The approval in adults was based on three randomised clinical trials which showed that treatment with remdesivir lead to clinically meaningful improvements across multiple outcomes compared to placebo. For instance, in the most recent ACTT-1 trial, published in the New England Journal of Medicine, remdesivir significantly improved time to recovery by 5 days and reduced disease progression among patients requiring oxygen. It also showed an improved time to recovery among patients not requiring oxygen in the SIMPLE-Moderate trial conducted in hospitalised patients. Moreover, adverse effects with remdesivir were similar to placebo.
Remdesivir was approved under the early access to medicines scheme in the UK in May 2020.
Reference
FDA News release. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-covid-19
The study by a team from the University of Maryland, Baltimore, analysed data for 412 patients admitted to hospital in several US states between March 2020 and July 2020. Included patients were 18 years and over with a positive PCR test result for COVID-19. Use was defined as administration within 24 hours of hospital admission or in the previous 7 days and any patients for whom aspirin was administered after an outcome, for example, mechanical ventilation, were considered in the non-aspirin group. The study’s primary outcome the need for invasive mechanical ventilation and secondary outcomes were intensive care admission and in-hospital mortality. The rational for the primary outcome was based on the drug’s ability to irreversibly inhibit platelet aggregation in the lungs and thus reduce pulmonary microthrombi and subsequent lung injury.
Findings
For the 412 patients included, the mean age was 55 years and 59% were male. In total, 98 (23.7%) of patients received aspirin with a median dose of 81mg and 75% of these were taking the drug prior to hospital admission and 86% took aspirin 24 hours prior to admission. Admission vital and laboratory values were not significantly different between the aspirin and non-aspirin groups. After adjustment for potential confounders, use of aspirin significantly reduce the need for invasive mechanical ventilation (adjusted hazard ratio, HR = 0.56, 95% CI 0.37–0.85, p = 0.007). For the secondary outcomes, aspirin use reduced the risk for intensive care (HR = 0.57, 95% CI 0.38–0.85, p = 0.005) and in-hospital mortality (HR = 0.53, 95% CI 0.31–0.90, p = 0.02).
Commenting on the results, the authors suggested that the drug was a potentially useful adjunctive treatment in patients with COVID-19 and called for further studies to confirm these findings.
Reference
Chow JHM et al. Aspirin use is associated with decreased mechanical ventilation, ICU admission and in-hospital mortality in hospitalised patients with COVID-19. Anesth Analg 2020 doi: 10.1213/ANE.0000000000005292
The REACT-1 study was established in May 2020 by a team from Imperial College, London and involves obtaining nose and throat swabs from non-overlapping random samples of the population of England, at ages 5 years and above, obtained from a list of GP registered patients as the sampling frame. The swabs are sent to patient’s homes and collected via courier and PCR tested. To date there have been five rounds of data collection and the team use this data to analyse trends in swab positivity and provide weighted and unweighted population estimates. The latest publication includes data from round 6, collected from 16 to 25 October 2020 and is therefore as current as possible.
Findings
In the latest round there were 863 positive swabs from a total of 85,971, giving an unweighted prevalence of 1% and a weighted prevalence of 1.28% (95% CI 1.15–1.41%). Compared to round 5 (18 September to 5 October 2020) where the weighted prevalence of was 0.60%, the latest figures suggest that the prevalence of COVID-19 has more than doubled. Putting the data into perspective, the authors estimate that around 960,000 individuals have the virus on any one day and that this will lead to approximately 96,000 new infections per day. Interestingly, this latest weighted prevalence is the highest recorded compared to earlier rounds. For instance, the paper reports that in round 1 (1 May to 1 April 2020), the weighted prevalence was 0.16%. Additionally, the latest figures indicate that the prevalence was highest in Yorkshire and the Humber at 2.72% and lowest in the East of England at 0.55%. Epidemic growth is no longer fastest in the North of England but is increasing in the South East, East of England, London and the South West. Furthermore, prevalence has increased across all age groups with the greatest increase now among those aged 55–64, up threefold from round 5 although the highest weighted prevalence remains in the 18–24-year-olds at 2.25% an increase from 1.59% in round 5.
This increased prevalence gave an average R number of the period of rounds 5 and 6 of 1.20. The authors note that their most recent data suggests a national doubling of infection rates every 9 days and that this corresponds to an R value of 1.56. They conclude by stating that the epidemic has now reached a critical stage and that it is time to introduce more stringent measures to control the virus and thus avoid more hospital admissions and deaths.
Reference
Riley S et al. High prevalence of SARS-CoV-2 positivity and increasing R number in England during October 2020: REACT-1 round 6 interim report. MedRxiv 2020. https://doi.org/10.1101/2020.09.30.20204727
23rd October 2020
To date only two clinical trials have examined the value of convalescent plasma therapy (CP) in patients with COVID-19 though both were stopped early and did not appear to show any significant benefit. For this new study, researchers from the Indian Council of Medical Research have undertaken a randomised trial in over 400 patients but the results also suggest that CP is of limited value. The study recruited 464 adult patients (aged 18 and over) with a median age of 52 years (75% male) from 39 public and private hospitals across India who were admitted to hospital with confirmed moderate COVID-19, based on a positive PCR test. Included patients had a partial pressure of oxygen in arterial blood/fraction of inspired oxygen (Pa02/FiO2) ratio between 200mmHg and 300mmHg, or a respiratory rate of more than 24/minute and an oxygen saturation < 93%. Eligible CP donors were required to have had a PCT positive test for COVID-19 and symptom resolution for 28 consecutive days before donation or a 14-day period which included two negative PCR tests collected 24 hours apart.
Patients were randomised to either CP and best standard of care (intervention group) or care lone (the control group) and intervention patients received two doses of 200ml CP transfused 24 hours apart. The primary outcome as a composite of progression to severe disease Pa02/FiO2 ratio < 100mmHg, anytime within 28 days of enrolment or mortality at 28 days.
Findings
Progression to severe disease occurred in 19% vs 18% (intervention vs control) and 28 day mortality occurred in 15% vs 14% (intervention vs control) of patients. There was a statistically significant higher proportion of patients receiving CP with a resolution of shortness of breath after 7 days (76% vs 66%) and fatigue (73% vs 60%), there was no difference for fever or cough. In addition, significantly more patients (68% vs 55%) had a negative PCR test at day 7. The authors concluded that as a treatment for COVID-19, CP appeared to be of limited value.
Reference
Agarwal A et al. Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial). BMJ 2020;371:m3939.
Patients with type 2 diabetes have also been shown to have an increased the risk of cognitive impairment and dementia. Achievement of good glycaemic control is associated with a reduction in the risk of many of adverse health outcomes and this can be attained through weight loss, but the evidence for an improvement in cognitive impairment is currently mixed. In this study, researchers from several centres in the US have reported on the results from the Action for Health in Diabetes (look AHEAD) study which suggests that it is glycaemic control, rather than weight reduction, which has the greatest impact on cognitive functioning. The look AHEAD study is a single blind, randomised trial that recruited 5145 individuals during 2001 to 2004 with a BMI >25kg/m2, a HbA1c < 11%, triglycerides < 600mg/dl and a systolic/diastolic blood pressure < 160/100 mmHg. Participants were randomised to either an intensive lifestyle intervention (ILI) or a diabetes support and education (DSE) control group and the interventions continued until 2012, which was an average of 9.9 years. For the cognitive assessment arm, 1089 participants from the original study were recruited at year 8 or 9 of follow-up and undertook 2 or 3 cognitive assessments, that evaluated verbal learning, memory, speed of processing, executive function and global cognitive functioning.
Findings
There was an equal number of participants from the ILI and DSE groups; the mean age of both samples was 58 years, and 42% of both groups was male and roughly 10% had pre-existing cardiovascular disease. Improvements in blood sugar control was associated with greater improvements in cognitive scores for most measures. In contrast, the association between improvements in weight loss and cognitive scores was less clear and depended to some extent, on the cognitive measure.
The authors were unable to account for these findings and concluded that any improvements in cognitive function were largely dependent on baseline levels of adiposity and cardiovascular disease history.
Reference
Carmichael OT et al. Long-term change in physiological markers and cognitive performance in type 2 diabetes: the look AHEAD trial. J Clin Endrocrinol Metab 2020; doi:10.1210/clinem/dgaa591
This information is also important to inform the requirements for in-patient and outpatient isolation and it is necessary to gain a better insight of the potential significance of positive PCR tests over longer periods of time. Now researchers from the Division of Infectious Diseases, Oregon University, have undertaken a review of published data to determine the duration of viral shedding among those infected with COVID-19 and their findings have implications for the risk of transmission. The team queries public databases including PubMed, LitCoVID, the WHO COVID-19 literature repository and Google scholar for relevant articles. In each case, the articles were reviewed and assessed in terms of the design, population, healthcare setting, diagnostic testing methods and patient symptoms and illness severity.
Findings
A total of 77 studies were eligible for analysis and included prospective case studies, retrospective series, case reports, point prevalence studies and position statements. Only 59 studies were peer-reviewed, 6 were pre-prints and 13 researcher letters or a letter to the editor of a journal and 70 of the studies described hospitalised patients. All of the studies reported PCR-based assessment of viral shedding and 12 studies reported viral culture data. In terms of viral shedding, the data revealed that the duration ranged from a minimum of 1 day to 83 days although the pooled median duration of RNA shedding from respiratory samples based on 28 studies was 18.4 days (95% CI 15.5–21.3 days). When stratifying by disease severity, the median duration of RNA shedding was 17.2 days (95% CI 14–20.5 days) for those with mild to moderate disease and 19.8 days (95% CI 16.2–23.5 days) for those with severe disease. In general terms, the authors found that viral loads were highest within 1–2 weeks of illness onset but declined gradually although this rarely extended past 25 days. In discussing their results, the authors noted that while PCR positive tests can be prolonged, viral culture data suggested that viable virus samples could only be obtained from between 6 days prior to symptom onset but no later than 20 days after.
Reference
Fontana L et al. Understanding viral shedding of SARS-CoV-2: review of current literature. Infect Control Hosp Epidemiol 2020;1-35. doi:10.1017/ice.2020.1273
19th October 2020
In two of the previous cases, the level of symptoms were much less upon re-infection; however, for the latest case study, symptoms were much worse with the second infection.
The case was reported by a team from the Nevada Institute of Personalised Medicine, USA and relates to a 25-year old man with no underlying health issues or use of immunosuppressant therapy. His initial infection was towards the end of March and a positive PCR test for COVID-19 was obtained on the 18 April 2020 though his symptoms resolved after a month. The patient continued to feel well until the end of May 2020 when he re-presented to health services and found to be hypoxic with shortness of breath and admitted to hospital and required ongoing oxygen support while hospitalised. A second PCR COVID-19 test in early June was also positive although an antibody test was also performed which detected IgG and IgM antibodies against COVID-19. Viral material from the second PCR test was collected and subjected to genomic sequencing.
Findings
The genomic analysis revealed that the two viral samples were significantly genetically distinct. In addition, the authors performed a survey of COVID-19 strains identified within the Nevada area which revealed that both genotypes were in circulation. Thus the patient was infected with a different strain of COVID-19 on both occasions although the latter infection appeared to be more virulent. In commenting on their findings, the authors noted that the results had important implications for vaccine development in that the initial infection was unable to generate a sufficient immune response to against the subsequent episode of infectivity. However, a recognised limitation was that they were unable to assess the patients’ immune response after the first infection.
The authors called for further work on genomic sequencing of positive cases to enable effective health surveillance to help identify any such cases of COVID-19 re-infection in the future.
Reference
Tillett RL et al. Genomic evidence for reinfection with SARS-CoV-2: a case study. Lancet Infect Dis 2020; https://doi.org/10.1016/ S1473-3099(20)30764-7
12th October 2020
The discovery of an effective treatment will most likely bring huge financial gains for the organisation or company who succeed in finding the silver bullet. All research groups will be acutely aware of the rapid pace of change in COVID-19 research and the pressure to achieve and disseminate their findings. In their haste to get articles to press, scientists have literally inundated journals with manuscripts and ‘pre-prints’ have become much more readily available. In addition, many journals are now offering open access to their articles with the result that any initial positive results are widely disseminated in the lay media, spreading hope that these latest findings will bring salvation from the ravages of COVID-19. Moreover, a heightened desire to achieve success among the scientific community and the prospect of further grants based on positive research findings, serves only to increase the pressure upon those workers, with the attendant risk for not only an honest error but even blatant misconduct.
Nevertheless, utilising the findings of ‘pre-print’ COVID-19 research articles to aid clinical decision-making process is an inherently dangerous practice, especially as these findings have not been subjected to peer-review. In fact, the pre-print sites do caution that an article contains preliminary findings yet despite this cautionary note, clinicians sometimes appear to throw caution to the wind and seek to change clinical practice based on positive early data. This has been illustrated with the 4-aminoquinolones, hydroxychloroquine and chloroquine, mooted as treatments for COVID-19. Both drugs has been used for many years as anti-malarials and hydroxychloroquine has also proved to be of value a disease-modifying drug for the management rheumatic diseases. The original hope that hydroxychloroquine might represent a promising treatment for COVID-19, arose out of laboratory studies of its potential anti-viral activity. Animal studies showed that 4-aminoquinolones demonstrated anti-viral activity against both avian influenza A H4N1 and the Zika virus.1,2 Nonetheless, while chloroquine demonstrated in-vitro activity against influenza, it failed to provide protection against influenza in a large, randomised trial.3 At the outset of the pandemic, several small trials in China reported that hydroxychloroquine seemed beneficial and on 28 March 2020, the food and drug administration (FDA) in the US, approved the use of hydroxychloroquine for COVID-19 under its emergency use authorisation process. In May 2020, however, a large, registry-based analysis published in the Lancet that included 3016 patients receiving hydroxychloroquine, found that the drug increased the risk of death.4 Although the Lancet later retracted the paper after an independent review found that not all the necessary data was available, the FDA also revoked the emergency use authorisation for chloroquine and hydroxychloroquine on 15 June 20205. As noted by Kim et al,6 a rapid dissemination in the lay press and social media, combined with endorsement by prominent political figures, created a surge in demand for hydroxychloroquine despite an initial over-interpretation of the data and lack of direct supporting evidence of its value. This example serves to highlight our desperate need for an effective drug even where there is lack of credible evidence. A further issue which has not received much public attention is how in a number of cases, pre-print articles are never published and, in some cases even retracted.
Retracted publications
According to the US ClinicalTrials.gov site, there are currently 2548 COVID-19 clinical studies registered7 and over the last few months this has led to an enormous amount of pre-published material. Though it is inevitable that some studies fail to successful pass the peer-review process an increasing number are being retracted. According to the website ‘Retraction Watch’, currently 34 COVID-19-related publications have been retracted, three temporarily retracted, and for two articles there have been expressions of concern.8 The latter category (expression of concern) although not strictly a retraction, does alert readers that there are potential integrity issues with the paper. Although the reasons for a retraction are not always clear, it is invariably the authors themselves who instigate the retraction possibly due to more quality reporting. In fact, an analysis of COVID-19 treatment trials by researchers from the Oxford Centre for Evidence-based Medicine (CEBM) noted how too many of the current COVID-19 trials are open-labelled and too few double-blind, leading to biased results that can distort therapeutic decision-making.9
The vast number of research studies seeking approval has meant that ethics committees are deluged with COVID-19 study applications. Furthermore, these committees are unlikely to have members with the necessary specialist knowledge from key areas such as virology or immunology to critically appraise the applications. In a recently published communication in the Journal of Medical Ethics, Bramstedt10 has worryingly identified a large number of international COVID-19 studies that have been withdrawn as ‘pre-prints’ and some even after full publication.
It seems increasingly likely that the current pandemic will remain with us for several months and as new discoveries about the virus and possible treatments emerge, there will be a continued rush by researchers to publish their findings. However, it is important to avoid what has been termed ‘hot stuff bias’ in which investigators become less critical in their approach to researching a fashionable topic and journals more likely to publish findings on the topic.11
As COVID-19 continues to kill thousands of people across the globe, the research community has a duty to ensure that it undertakes high quality work that if used to inform clinical decision-making does not lead to either patient harm or provide a limited benefit. The ongoing UK RECOVERY trial demonstrates that large-scale, high quality research into COVID-19 is possible and likely to yield reliable results. Moving forward, this latter trial should serve as a template for future studies and hopefully reduce the amount of substandard research that is ultimately retracted.
References
9th October 2020
It is thought that skin transmission is just one of many potential routes although little is known about how long the virus can survive on the surface of not only skin or other surfaces. In a new study by a team from the Department of Infectious Diseases, Kyoto University, Japan, researchers used skin samples obtained from forensic autopsy samples, collected one day after death and found that the virus can survive for several hours but that it is quickly eliminated after washing with a disinfectant. The team used influenza virus (IV) for comparative purposes but also examined the survival of both viruses on several difference surface materials such as stainless steel, glass and polystyrene. The survival of the viral samples on these different surfaces were also examined after being mixed with mucus samples. In all cases, the samples were incubated at 25oC for 30 minutes and the content of both influenza and COVID-19 analysed.
Findings
The results showed that COVID-19 survived for considerably longer than IV on all tested surfaces. For example, IV survived for up to 11 hours on stainless steel compared to 85 hours for COVID-19. The virus also survived for a similar time on glass but for only 58 hours on polystyrene. In contrast, COVID-19 managed to survive for only 25 hours on stainless steel compared and for nearly 24 hours on glass when mixed with mucus. When directly in contact with human skin, COVID-19 survived for 9 hours compared to 1.82 hours for IV but this was reduced to only 4 hours when in mucus. However, mixing with 80% ethanol reduced COVID-19 survival time in mucus to less than 15 seconds.
Commenting on their findings, the authors noted that because COVID-19 can survive for up to 9 hours on human skin it poses a significant risk for transmission but the study also highlighted the importance of hand washing with ethanol which inactivated both COVID-19 and IV viral particles within less than 20 seconds.
Reference
Hirose R et al. Survival of SARS-CoV-2 and Influenza virus on the human skin: importance of hand hygiene in COVID-19. Clin Infect Dis 2020; https://doi.org/10.1093/cid/ciaa1517
Consequently, researchers often use a combination of objective and subjective measures when assessing the response to treatment. For instance, it is known that subjective measures, for example, pain scores can be high, hence the need for independent, objective measures. However, in a new analysis of the placebo response among patients in trials for rheumatoid arthritis therapies, a team from the Brigham and Women’s Hospital, Boston, USA, found significant improvements in both measures. The team examined the placebo arm responses for five double-blind trials conducted internationally of at least 24 weeks duration between 2005 and 2009 among patients with rheumatoid arthritis. They extracted the individual level patient data from trials and focused on pain scores (subjective) and C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values, both of which are objective measures. Pain scores were assessed using a standardised measure, namely a 0 to 100 mm visual analogue scale (VAS) and CPR and ESR were measured by blood testing. As some patients in the trials crossed-over to the active treatment, the researchers pre-selected 12 weeks from baseline to assess responses. Study medications included methotrexate and other disease-modifying antirheumatics.
Findings
The data set included 788 patients (82% women) with a mean age of 51 years. There was a statistically significant reduction in pain intensity (-14mm, 95% CI – 12 to 16 mm), CRP levels (-0.51mg/dl 95% CI -0.47 to -0.56) and ESR (-11mm/h, 95% CI -10 to -12), all with p values less than 0.001. Commenting on their findings, the authors were surprised by the clinically meaningful reductions in subjective and objective measures observed in placebo participants, indicating that it was more than a psychological placebo effect.
Furthermore, the cautioned that simply using objective rather than subjective measures in future trials would not necessarily lead to clearer results and that there was a need to further understand the effect of confounding factors and baseline covariates in placebo responders.
Reference
Vollett J et al. Assessment of placebo response in objective and subjective outcome measures in rheumatoid arthritis clinical trials. JAMA Netw Open 2020;3(9):e2013196. doi:10.1001/jamanetworkopen.2020.13196
IMPORTANT LINKS
MORE FROM COGORA
© Cogora 2025
Cogora Limited. 1 Giltspur Street, London EC1A 9DD
Registered in the United Kingdom. Reg. No. 2147432
