COVID-19 survives for up to 9 hours on skin surfaces but quickly removed by washing

9th October 2020

Knowledge of how long COVID-19 can survive on various surfaces is important in assess the possible routes for transmission.

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

Large placebo response in subjective and objective measures in RA trials

It is largely expected that in a randomised, double-blind clinical trial, individuals assigned to placebo will experience some level of improvement in relevant outcomes and this can lead to an underestimation of the effectiveness of the therapy being tested.

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

AI predicts COVID-19 status before a PCR test

Current testing for COVID-19 relies on a PCR test using nasopharyngeal swabs although results can take up to 48 hours and sometimes even longer.

Now a team from Weill Cornell Medicine, New York, has created an artificial intelligence (AI) system that can use routine test data results to determine if a patient has COVID-19. Normally, clinicians order a battery of blood tests in addition to a PCR test, including routine laboratory tests and a chest X-ray and these results are generally available within 1 – 2 hours. Researchers therefore hypothesised if the results of the routine laboratory test could be used to predict if someone was infected with COVID-19 without the PCR test. The included patient demographics such as age, sex, race into a machine learning model and incorporated the results for 27 routine tests. The laboratory results were made available two days before the PCR test result. The dataset included a total of 5893 patients admitted to hospital between March and April 2020 and they excluded individuals under 18 years of age and those who PCR result was inconclusive and patients without laboratory test results within two days prior to the PCR test.

Findings
A total of 3356 patients who were tested for COVID-19 were included with a mean age of 56 years of whom, 1402 were positive and 54% emergency department admissions. Using a machine learning technique known as a gradient boosting decision tree, overall, the algorithm identified COVID-19 positivity with a sensitivity of 76% and a specificity of 81%. However, limiting the analysis to emergency department patients, increased the sensitivity to 80% and the specificity to 83%. Moreover, the algorithm correctly identified those who had a negative COVID-19 test result. A recognised limitation was the testing was specific those admitted to hospital with moderate to severe disease and thus requires further work to identify milder cases.

Nevertheless, the authors concluded that their algorithm is potentially of value in identifying whether patients have COVID-19 before they receive the results of a PCR test.

Reference
Yang HS et al. Routine laboratory blood tests predict SARS-CoV-2 infection using machine learning. Clin Chem 2020; https://doi.org/10.1093/clinchem/hvaa200

Individuals with loss of smell more likely to have COVID-19 antibodies

5th October 2020

Although a loss of taste or smell (anosmia) has been added to the list of COVID-19 symptoms, a new study conducted before anosmia was added to the list, serves to highlight the importance of these symptoms.

The results showed that individuals who experience loss of smell were three times more likely to have COVID-19 antibodies than those with isolated taste loss. In this newly published study, researchers from University College London, recruited individuals between April and May 2020, when anosmia was not recognised as a symptom of COVID-19. Adults registered with four primary care centres in London were sent a text message asking whether their sense of taste or smell had reduced in the last month. Those answering yes were directed to an online questionnaire which collected demographics and other information and were sent a point-of-care antibody testing kit. Participants then held a video consultation with a healthcare professional who supervision collection of a whole blood sample from a finger-prick test.

Findings
A total of 33,650 text messages were sent and 590 participants recruited, of whom 567 (96%) had an antibody test and the mean age of the sample was 39.4 years (69.1% female). Among the 567 individuals, 78% of tested positive with 93.4% reporting either a complete or partial loss of a sense of smell and 90.2% either a complete or partial loss of taste. Interestingly, 40% of those testing positive had neither a cough or fever. In regression analysis, participants with a loss of smell alone were nearly three-times more likely than those with isolated taste loss to have COVID-19 antibodies (adjusted odds ratio, OR = 2.72, 95% CI 1.37 – 6.36, p < 0.001). Moreover, those with a combined loss of smell and taste were four-times (adjusted OR = 4.11, 95% CI 2.24 – 7.08, P < 0.001) to have COVID-19 antibodies.

Commenting on their findings, the authors noted that loss of smell was a highly specific symptom for COVID-19 and that this alone should be used as a criterion for self-isolation.

Reference
Makaronidis J et al. Seroprevalence of SARS-CoV-2 antibodies in people with an acute loss in their sense of smell and/or taste in a community-based population in London, UK: An observational cohort study. PloS Med 2020;17(10): e1003358. https://doi.org/10.1371/ journal.pmed.1003358

Short-term use of hydroxychloroquine safe in COVID

1st October 2020

Several drugs have been used in an effort to treat the symptoms of COVID-19 including anti-malarials such as hydroxychloroquine (HCQ) although there have been concerns expressed about the safety of the drug, in particular, its prolongation of the QT interval which is associated with arrhythmias.

Now in an analysis by the European Society of Cardiology, it appears that HCQ can be safely administered for a short period of time in a range of clinical settings. The authors examined the effects of HCQ in three different settings: home management; medical wards; and intensive care units. For patients managed at home, the drug was initiated in a hospital setting. Eligible patients were required to have a pre-HCQ 12-lead ECG available and a second ECG which was defined as early (within 5 days before the first dose of HCQ) or late (either 36-72 hours or 96 hours after the first dose). For all patients, various parameters were collected including demographics, cardiovascular comorbidities, ECG readings et and stored in a de-identified database. The team also collected PQ, QRS and QTc durations before and after HCQ administration as well as ventricular arrhythmic events from healthcare records. Arrhythmia safety was assessed with regard to malignant QT-prolong arrhythmias. In cases where patients had died, a committee of three members (blinded to the treatment at the time of occurrence of the arrhythmic event) judged the relationship with HCQ administration.

Findings
In total, 649 patients were enrolled with a mean age of 61.9 years (46% male) and HCQ was administered at home (19.4%), in hospital wards (76.3%) and at intensive care units (4.3%). For patients with late ECG readings (36-72 hours and 96+ hours after the first dose), a significant QT/QTc interval prolongation was observed but the magnitude of the increase was modest at +13 ms. In addition, baseline QT/QTc length and the presence of fever at admission were the most important determinants of QT/QTc prolongation and there were no arrhythmic-related deaths reported. The incidence of ventricular arrhythmias was low (1.1%) and these events were found to be not related to QT or HCQ therapy. Finally, the authors reported no difference in QT/QTc prolongation across the different settings.

They concluded that HCQ is safe in the short-term for those with COVID-19 provided that a baseline ECG is taken and a patient risk assessment performed.

Reference
Gasperetti A et al. Arrhythmic safety of hydroxychloroquine in COVID-19 patients from different clinical settings. Europace 2020;0, 1–9 doi:10.1093/europace/euaa216

Study suggests UK COVID-19 infection rates are falling

The Real-time Assessment of Community Transmission-1 (REACT-1) study was established by researchers from Imperial College, London, in May 2020, to track the prevalence of COVID-19 in the community in England, as the country ended lockdown.

Although previous reports from the REACT-1 team reported falls in the prevalence of COVID-19 between May and early August, by mid-August, they detected an upturn in the rate of infection and estimated the R value to be around 1.7. In their latest report, which covers the period from 18 to 26 September, the numbers suggest that there is some indication that the rate of increase in the prevalence may have slowed. The REACT-1 study uses repeated random samples of the population between the ages of 5 and over-using the NHS list of patients registered with a GP. Identified individuals are contacted by post and asked to complete a registration questionnaire and are provided with a self-administered swab kit which are collected from participants and tested using PCR for the presence of the virus. The team calculate the prevalence as a ratio of positive tests to overall tests and correct this figure for age, sex, region, ethnicity.

Findings
The latest report summarises the findings from the first four rounds and interim data for the 5th round. To date over 680,000 swabs have been tested and for the most recent period, there were 363 positive tests from a sample of 84,610, giving a weighted prevalence of 0.55%. This figure represents an upward trend and is the highest prevalence since the beginning of the study. It allowed the authors to estimate a doubling time of 10.6 days, which corresponds to an R number of 1.47 and a prevalence of over 1 in 200 across the population of England.

The authors suggest that the data indicates the epidemic now reflects community transmission rather than through hospitals or care homes and concluded that there is an urgent need to redouble efforts to reduce community transmission.

Reference
Riley S et al. High prevalence of SARS-CoV-2 swabs positivity in England during September 2020: Interim report of round 5 of REACT-1 study.
www.imperial.ac.uk/medicine/research-and-impact/groups/react-study/real-time-assessment-of-community-transmission-findings/

Early introduction of gluten reduces incidence of coeliac disease

The enquiring about tolerance (EAT) study is an open-label randomised trial of a dietary intervention for the prevention of food allergy (including coeliac disease) in which potentially allergenic foods were introduced to an infant’s diet at an early age.

In the present study, a team from the Paediatric Allergy Research group, Kings College, London, focused on the development of coeliac disease at 3 years of age, after the introduction of gluten, a protein present in wheat that triggers the disease, from 4 months of age. A total of 1004 infants from the general population of England and Wales, were enrolled in the study and were all breast-fed until 13 weeks of age, after which they were randomised to consume six allergenic foods; cow’s milk, hen’s egg, peanut, sesame, cod fish and wheat in addition to breast milk (intervention group) or to continue with exclusively with breast milk until 6 months of age (control group), as recommended by UK government guidelines. The weekly recommended dose of wheat for a child was set at 4g of wheat protein and this was provided as wheat-based cereal biscuits (Weetabix) or equivalent. The team calculated that this was equivalent to a gluten dose of 3.2g/week and though this was set as the minimum intake, no maximum limits were set. The families were asked to complete weekly questionnaires through to 1 year and then every 3 months until 3 years of age.

Findings
For the 1004 (488 given the allergenic foods) infants included in the final analysis, 514 were male (51.2%) and the mean gluten intake between ages 4 and 6 months was 0.49g/week for the control group compared to 2.66g/week for the intervention group. At 8 months of age, gluten consumption had increased to 8.21g/week in the intervention group. Interesting by 3 years of age, 7 children in the control group but none of those in the gluten group, at developed coeliac disease.

Given the relatively small sample size, the authors called for more studies to confirm whether early introduction of gluten is an effective strategy to prevent the development of coeliac disease.

Reference
Logan K et al. Early gluten introduction and celiac disease in the EAT study. A prespecified analysis of the EAT randomised clinical trial. JAMA Pediatr doi:10.1001/jamapediatrics.2020.2893

More evidence for the protective effect of vitamin D in COVID-19

29th September 2020

Much has been written during the current pandemic inferring that vitamin D has a protective role against COVID-19.

Although in a recent review, NICE concluded that there was no evidence to support either a preventative or treatment role for vitamin D, new evidence from an analysis of a large patient cohort, suggests an inverse relationship between levels and positive COVID-19 status, implying that the vitamin has a protective role.

A team of US researchers retrospectively analysed a large, anonymous patient data set 50 US states and the District of Columbia between March and June 2020, for whom 25-hydroxyvitamin D (25(OH)D) levels were recorded in the previous 12 months. They limited their analysis to one COVID-19 test result per patient and included all available demographics including ethnicity and categorised 25(OH)D status as either low (<20ng/ml), adequate (30-34ng/ml) or higher ( >60ng/ml).

Findings
In total, 191,779 patients were included with a mean age was 54 years (68% female) and overall the COVID-19 positivity rate was 9.3%. When examining the relationship between 25(OH)D levels and COVID-19 positivity, the rate was highest among those with a low vitamin D status (12.5%) and decreased as it improved, being 8.1% for those with adequate levels and 5.9% among those with the highest levels.

In terms of ethnicity, COVID-19 positive rates were highest in black individuals (15.7%) compared to Hispanics (12.8%) and lowest in white, non-Hispanics (7.2%, p< 0.001 for both comparisons). Furthermore, the difference in positivity rates between ethnic groups was reflected in mean 25(OH)D levels, which were 33.0 vs 29.1 vs 28.8 ng/ml for white, blacks and Hispanic individuals (p< 0.001) respectively. In regression analysis, there was a strong association between vitamin D levels and lower COVID-19 after adjustment for all demographic factors (adjusted odds ratio = 0.98 per ng/ml increment).

The authors concluded that their findings provide a further rationale to explore the role of vitamin D supplementation to reduce the risk of COVID-19 infection.

Reference
Kaufman HW et al. SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels. PLoS ONE 15(9): e0239252. https://doi.org/ 10.1371/journal.pone.0239252

Study analyses immune response to COVID-19 in young people

A good deal of evidence points to children having a less severe form of COVID-19 and childhood mortality is rare. Although age-related factors impact on disease severity, the reasons why children experience less severe illness is uncertain.

Now a new study by a team from the Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, suggests that these differences are linked to a more robust innate immune response to the virus from children. Researchers compared the clinical characteristics and outcomes among a group of 65 young people (aged under 24 years) and 60 adults over 24 years of age who were hospitalised with COVID-19 by measuring various cytokine, humoral and cellular immune response markers.

Findings
Overall, paediatric patients had the shortest length of hospital stay and lower mortality than the adults. In general terms, there was an inverse relationship between age and levels of interleukin-17A (IL-17A) and interferon gamma (ING) but not for interleukin-6 and tumour necrosis factor alpha. Adult patients also mounted a stronger T cell response to the viral spike protein as determined by higher levels of CD25+ on CD+ T cells and the frequency of ING and CD4+ T cells. Commenting on their results, the authors noted that the poorer outcomes for adults were not related to a failure to generate a sufficient T cell or antibody response to the virus but more likely to be due to a stronger IL-17A response in children. The authors also speculated that this may contribute more towards immune protection against lung disease, which was far less severe in children.

In other words, the data suggest that because children appeared to be able to generate a stronger innate immune response than adults, this may be protective against the progressive cytokine release caused by the virus, leading to rapid resolution of infection.

Reference
Pierce CA et al. Immune responses to SARS-CoV-2 infection in hospitalised pediatric and adult patients. Sci Transl Med 2020; 10.1126/scitranslmed.abd5487

US study finds nosocomial infection of COVID-19 is rare

25th September 2020

With many patients unwilling to visit hospitals due to the risk of becoming infected with COVID-19, what are the risk of nosocomial (that is, hospital-acquired) infection within the hospital environment?

This was the question posed in a new study by a team from the Department of Population Medicine, Harvard Medical School who sought to determine the incidence of COVID-19 in a large, 793-bed hospital in Boston. They identified all patients who were hospitalised from 7 March 2020 through to 17 June 2020, including those who were admitted because of COVID-19, which was defined as a positive test during hospitalisation or within 14 days prior to admission. When assessing the extent of nosocomial infection, the authors reviewed medical records and only included those who tested positive on day 3 of their hospital stay or within 14 days after hospital discharge.

Findings
A total of 9149 patients with a mean age of 46.1 years (57.3% female), were admitted to the hospital during the study period, for whom 7394 COVID-19 tests were performed and of which 697 tested positive. However, of the 697 patients, only 12 (1.7%) were diagnosed on day 3 (or later) and the median time from admission to the first positive test result in these patients was 4 days (range 3 to 15 days). Interestingly, none of the 12 patients had known exposure to either staff or other patients who had tested positive for COVID-19. Analysis of medical records suggested that infection was definitely acquired before hospitalisation in 4 of the 12 cases and very likely for 7. Only a single patient was definitely infected in hospital because symptoms began on day 15. Post-discharge, among 8370 patients hospitalised with non-COVID-19-related conditions, 11 (0.1%) tested positive within 14 days and again, only a single case was deemed to have acquired the virus during their hospital stay and developed symptoms 4 days after discharge.

The authors concluded that the hospital had robust and rigorous infection control practices and suggested that these results should reassure patient that nosocomial infection is a rare event.

Reference
Rhee C et al. Incidence of nosocomial COVID-19 in patients hospitalised at a large US academic medical center. JAMA Netw Open 2020; 3(9):e2020498. doi:10.1001/jamanetworkopen.2020.20498