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6th May 2020
Recent research had suggested that more than one type of SARS-CoV-2 was now circulating in the pandemic, with one strain being more aggressive and causing more serious illness than the other.
Now, using analysis of SARS-CoV-2 virus samples from the pandemic, scientists have been able to show that only one type of the virus is currently circulating. Their research is published in the journal Virus Evolution.
Viruses, including the one causing COVID-19, naturally accumulate mutations – or changes – in their genetic sequence as they spread through populations. However, most of these changes will have no effect on the virus biology or the aggressiveness of the disease they cause.
Earlier this year, it was reported that scientists had found two or three strains of SARS-CoV-2 circulating in the population, evidenced by certain mutations that had been detected. However, thanks to extensive analysis of the virus genomes annotated by the MRC-University of Glasgow Centre for Virus Research’s CoV-GLUE resource, scientists at the University of Glasgow have demonstrated that these detected mutations are unlikely to have any functional significance, and importantly, don’t represent different virus types.
CoV-GLUE tracks SARS-CoV-2’s amino acid replacements, insertions and deletions, which have been observed in samples from the pandemic. To date the database has catalogued 7237 mutations in the pandemic. While this may sound like a lot of change, scientists confirm that it is a relatively low rate of evolution for an RNA virus, and they expect more mutations will continue to accumulate as the pandemic continues.
On average, most observed mutations would be expected to have no, or minimal consequence to the virus’s biology. However, tracking these changes can help scientists better understand the virus pandemic and how COVID-19 is spreading in the community.
Dr Oscar MacLean, from the MRC-University of Glasgow Centre for Virus Research, said: “By analysing the extensive genetic sequence variation present in the genomes of the SARS-CoV-2 virus, the evolutionary analysis shows why these claims that multiple types of the virus are currently circulating are unfounded.”
“It is important people are not concerned about virus mutations – these are normal and expected as a virus passes through a population. However, these mutations can be useful as they allow us to track transmission history and understand the historic pattern of global spread.”
However, it is also suggested that the guideline may be relevant to newborn babies less than 72 hours old and 18-24-year-olds accessing healthcare services.
NG174 defines children and young people who are immunocompromised as those with:
NG174 focuses on what can be stopped or started during the pandemic and should be used alongside any other relevant professional guidance.
Patient communication and minimising infection risk
NG174 discusses the importance of communicating with patients, their families and carers to support their mental wellbeing during the COVID-19 pandemic to alleviate any anxieties or concerns they might have about the virus. The guideline suggests signposting patients to relevant charities and support groups including the NHS guidance on mental health and wellbeing aspects of COVID-19, NHS volunteer responders and the Royal College of Paediatrics and child health resources for parents and carers.
NG174 suggests that staff disseminate the fact that COVID-19 infections are usually mild and self-limiting in children even those who are immunocompromised. Patients are advised to continue to attend any scheduled appointments unless informed otherwise. Where a patient suspects COVID-19 infected, they are advised to contact their specialist teams to enable an appropriate assessment. Alternatively or if they are unable to contact the team, they must contact the NHS111 online coronavirus service but if seriously ill to contact emergency services.
NG174 advises on the need to minimise face-to-face consultations and make use of either via telephone or video instead or to contact patients via email or text messaging. Use of electronic rather than paper prescriptions is also suggested as is the need for alternative delivery routes for prescriptions and medicines such as pharmacy delivery services, via the post, using NHS volunteers or drive through medicine pick-up points. Patients are advised to maintain a current list of all treatments and a copy of their latest clinic letter to help healthcare staff should they require any treatment for COVID-19.
Shielding
NG174 advises patients and their parents to seek individual advice from their teams if they are in a designated shielded group and directs staff to further guidance from the Royal College of Paediatrics and Child Health shielding guidance and the UK government advice on shielding and social distancing.
Safeguarding
NG174 advises clinical staff to be familiar with any safeguarding concerns for patients, especially those deemed vulnerable and to use clinical discretion when advising on shielding and school attendance. The guideline signposts staff to the UK government guidance on supporting children and young people during the COVID-19 outbreak.
Where parents or carers have COVID-19
NG174 suggests that clinical staff work with parents or carers to develop appropriate plans for a child with complex needs should they parent/carer become infected with COVID-19. Such plans should include details of who might provide treatments and any training or support that they might be required.
Managing an underlying condition when the patient is not known to have COVID-19
When face-to-face appointments are required, patients should attend with a single family member and to avoid public transport if possible. NG174 recommends that staff inform parents of the need to inform the department prior to appointments if they or the patient has any COVID-19 symptoms. Staff are advised to triage the patient’s care and either rearrange or cancel appointments or ask them to attend as a suspected COVID-19 patient (see below). Home visits are a suggested alternative if possible, provided staff follow UK government guidance on infection prevention and control.
NG174 advises that where face-to-face appointments are required, staff aim to minimise the time patients spend in the waiting area through careful scheduling of appointments, discouraging early attendance and that patients remain in their transport vehicle until they receive a text message informing them that they are ready to be seen.
Once at the department, NG174 strongly recommends a “clean route” through the hospital and that treatments and prescriptions are delivered and dispensed rapidly.
Starting treatments affecting the immune system
NG174 suggests that staff take account of the following when considering to start drugs which affect the immune system:
In cases where treatments affecting the immune system are currently used, NG174 advises continuation to minimise the risk of graft rejection, a relapse or flare. In such cases, NG174 suggests that staff explore changes to the dosage, mode of delivery/route of administration, frequency of monitoring frequency (if possible) and whether the monitoring can be done remotely.
Managing the underlying condition in patients known or suspected of having COVID-19
From a clinical perspective, NG174 reminds staff that children and young people often show either no or mild COVID-19 symptoms although immunocompromised individuals may be more vulnerable to the virus. COVID-19 can also be difficult to diagnose as symptoms can overlap with other disease and in patients prescribed drugs affecting the immune system, the infection can present with atypical symptoms.
A relevant point made in NG174 is that since COVID-19 affects children differently to adults, there may be less risk in starting or continuing with treatments affecting the immune response.
NG174 states that if patients develop any red flags e.g. sepsis, meningitis or febrile neutropenia, assess and treat them in line with usual care guidelines.
In the absence of red flags, NG174 advises following the government guidance on investigation and initial clinical management of possible cases which provides information on testing and isolating patients.
If COVID-19 has been identified, NG174 advises following the UK government guidance on infection prevention and control.
If COVID-19 is later diagnosed in a patient not previously isolated from admission, NG174 advises following the UK government guidance on management of exposed healthcare workers and patients in hospital setting.
Stopping usual treatment in those with symptoms of COVID-19
When considering stopping a patient’s usual care, NG174 suggests that staff contact specialist teams for urgent advice and that staff consider:
Modification to usual care
NG174 recommends that specialist centres modify usual care to reduce patient exposure to COVID-19 and to make best use of available resources. Where modification of a patient’s treatment is deemed necessary, this should be undertaken by a multi-disciplinary team and in light of their clinical circumstances and any relevant preferences and the reasoning behind the changes fully documented.
Supply of medicines
The guideline advises that teams plan how best to manage any potential disruptions to normal supply routes e.g. home care delivery services and to only supply sufficient amounts to meet patient’s clinical need. Repeat prescriptions for oral medicines or other at-home treatments should also be prescribed to avoid the need to visit the hospital.
Healthcare workers
NG174 suggests that all NHS staff involved in all aspects of patient care (including receiving, assessing and caring) who have known or suspected COVID-19 infection, follow the UK government guidance for infection prevention and control. In addition, any healthcare staff with known or suspected COVID-19 infection should self-isolate and not return to directly working with patients who are immunocompromised until:
NG174 does state that healthcare workers can return to work in other clinical areas after self-isolation provided they follow the UK government guidance for households with possible COVID-19 infection. If self-isolating staff are still able to work, suggested roles include undertaking telephone or video consultations and participation in virtual multidisciplinary meetings. These staff can also help identify patients who can be monitored remotely and those who might require more support as well as performing any routine tasks which can be done remotely.
NG174 is available online and interested readers should check this version for further updates.
However, missing from this list was obesity, which is all the more surprising given that the evidence for the impact of obesity on viral infections has been known about for several years. For instance, a 2011 study that examined risk factors for severe outcomes in patients with H1N1 (‘swine flu’), found that patients with those with obesity (body mass index, BMI >30kg/m2) had a 2.9-fold increased risk (that is, odds ratio = 2.9) for death from the virus.2 In addition, other work has shown that obesity is accompanied by an impaired ability to produce a protective immune response to influenza virus3 and that being overweight has a negative effect on lung function, which increases burden of respiratory disease.4
Research has shown that obesity is associated with a chronic and low-grade inflammation, characterised by an increased secretion of pro-inflammatory cytokines by adipocytes (fat cells) such as tumour necrosis factor and interleukin-6 and 12. It also seems that this low-grade inflammation, leads to immune cell dysfunction which may aggravate the symptoms of influenza infection.5 Furthermore, in comparison to lean subjects, obese individuals shed viral particles for a longer period of time.6 Studies in rodents indicates that obesity results in a reduced ability to generate an immune response to influzena A virus and that the virus is retained for a longer period of time in the body, producing greater viral diversity and the potential for the emergence of more virulent strains.7
With World Health Organization data indicating that 23% of women and 20% of men are obese in the European region,8 is it possible that obesity is an important co-morbidity for more severe disease in those with COVID-19 which has not emerged until now, as the virus spreads across the Western world?
A recently published retrospective analysis has attempted to investigate the association between BMI and the need for intensive mechanical ventilation (IMV) in those with COVID-19.9 The analysis was undertaken at a French hospital and included 124 patients admitted to intensive care with COVID-19 pneumonia. Patients were predominately male (73%) and with an average age of 60 years.
The authors used the need for IMV as a proxy measure for the severity of COVID-19 infection and found that this increased with body mass index such that nearly 90% of those with a BMI >35kg/m2 required ventilation. Logistic regression indicated that there was 3.45-fold higher (odds ratio, OR = 3.45) risk of requiring IMV for those with a BMI between 30 and 35kg/m2, although this result was not statistically significant. However, there was a 7.36-fold higher risk (OR = 7.36) among those with a BMI >35kg/m2 which was a significant result. A limitation of the study was that the authors were unable to analyse the effect of BMI on mortality because too few patients died.
Exactly why higher BMI levels increase the need for mechanical ventilation are unclear. Nevertheless, previous work has shown how obesity reduces both the thoracic expansion of lungs at full inflation10 and lung volumes11 and that the restrictive pattern induced by the combination of these two effects may be responsible. Although the study by Simonnet et al9 was retrospective in nature and included only a small number of patients, it does raise the possibility that obesity may be an important co-morbidity.
References
The in vitro activity of chloroquine against severe acute respiratory syndrome caused by the SARS virus (which is related to COVID-19) was first demonstrated in 2004,1 and more recently, an expert consensus group from Guangdong province in China has endorsed use of chloroquine at a dose of 500mg twice daily for 10 days in all patients with coronavirus pneumonia.2
However, chloroquine is associated with several adverse effects. In the short-term, it has been shown to prolong the QTc interval3 whereas there is evidence to suggest that with longer-term use the drug accumulates, leading to retinal toxicity4 and myopathy.5
The value of either chloroquine or hydroxychloroquine in patients with COVID-19 remains unclear. One recent small open label study observed a synergistic effect from a combination of hydroxychloroquine and azithromycin at clearing viral load after between three and six days.6 Nevertheless, in a statement on 3 April, the International Society of Antimicrobial Chemotherapy, expressed concerns that the article did not “meet the Society’s expected standard, especially relating to the lack of better explanation of the inclusion criteria and the triage of patients to ensure safety”.7
The most recent study to explore the efficacy of chloroquine, comes from a study in Brazil. Researchers conducted a double-blind trial to assess the drug’s efficacy in hospital patients with severe respiratory syndrome secondary to COVID-19 infection.8 The study included patients aged 18 years and over who were hospitalised with a clinical suspicion of COVID-19 infection. Patients received chloroquine at a dose of either 600mg twice daily for 10 days or 450mg twice daily on day 1 and then 450mg daily for 4 days. In addition to chloroquine, patients were also given azithromycin (500mg daily for 5 days) and oseltamivir 75mg twice daily for 5 days when influenza infection was suspected.
The primary outcome was a reduction in lethality (that is, death) by at least 50% in the higher dose group and was due to be assessed after 28 days. The study had intended to enrol 440 patients but had only recruited 81 (41 to the higher dose, 40 the lower dose) before the data safety monitoring board terminated the trial. After 13 days, 39% (16/41) patients in the high dose group died compared with 15% (6/40) in the low dose group. The high dose group also experienced more instances of QTc prolongation (18.9% vs 11.1%). Overall, the risk of death was 3.6 times higher in the high dose group, a result that was statistically significant. However, after adjusting for patient age, the risk reduced to 2.8 and was no longer significant. Based on these finding, the study group decided to immediately interrupt the high dose group and all patients were switched to the low dose.
The authors concluded that “no apparent benefit of CQ [chloroquine] was seen regarding lethality in our patients so far”.
While this trial was interrupted at an early stage, the results should be seen as a warning that chloroquine (and probably hydroxychloroquine) are not the purported wonder drugs for those with COVID-19. Whether several of the ongoing clinical trials (see example in reference 8) will provide a more definitive answer of the value of chloroquine in those with severe COVID-19, remains to be seen.
References
29th April 2020
The statement notes how allergic diseases such as asthma are among the most prevalent conditions in children, necessitating a guideline for the health professionals who are providing care for these patients. The statement provides six recommendations for the management of childhood allergies and immunodeficiencies based on current facts and existing evidence. The statement itself reviews the current available evidence on the use of allergy treatments in children.
Are children different to adults?
While everyone is potentially liable to infection with COVID-19 although older age is a major risk factor, the statement notes how it appears that the infection is often less severe in children and mortality rates are lower than for adults although precisely why this might be the case is unclear.
COVID-19 and allergies
The current statement does notes that while patients with asthma are listed among those who are at a high risk of infection, pre-existing allergies are not currently considered to be a risk factor. Nevertheless, whether asthma treatments affect an individual’s susceptibility to COVID-19 is also unclear. The statement discusses how much attention has been directed at oral corticosteroids and how these drugs may have immune modifying effects and thus increase the risk of infection. Nevertheless, the statement directs readers to national and international asthma societies which currently do not advocate stopping oral corticosteroids. The statement acknowledges that much less is known about the effects of inhaled corticosteroids but based on the available evidence, suggests that inhaled corticosteroids are unlikely to pose an increased risk of either acquiring COVID-19 or of causing a more severe infection.
Patients with immunodeficiencies
The statement suggests that because primary immunodeficiencies (PID) are congenital disorders, those with PID may constitute an at-risk group and advises that this patient group should be carefully followed-up during the COVID-19 pandemic. Although COVID-19 may pose a risk for children prescribed immunosuppressive treatments, the statement still recommends that these treatments are continued despite the paucity of data on the immune effects of COVID-19.
Facts and recommendations
The statement finishes with a series of six facts and recommendations based on these facts.
Recommendation one
Because children are at a lower risk, paediatric allergists are advised to gain control of a child’s current allergy symptoms and to ensure that patients follow the current recommendations for hygiene and social distancing to minimise the risk of infection.
2. Whenever possible, diminish or remove risk factors
Recommendation two
While not all asthma is allergic in nature, during a time when seasonal allergies are likely to become more common, it is especially important to ensure that patients gain control of their asthma because uncontrolled asthma represents a risk for more severe disease with COVID-19 infection.
3. Initial symptoms of seasonal allergy may be confused with mild flu-like infection
Recommendation three
The statements suggest that seasonal allergy symptoms can initially resemble flu, the common cold or even COVID-19. It therefore advises allergists remain vigilant to this fact and although they should not be over-suspicious, it is important not to miss COVID-19 in an allergic patient.
4. Treat allergic rhinitis patients according to usual guidelines
Recommendation four
In the absence of specific evidence that allergy treatments increase the risk of infection with COVID-19 or that there is a greater likelihood of more severe disease if infected, allergy specialists are advised to continue to treat their patients following usual care guidelines. One exception noted in the statement is that treatment with biologics should be withheld because this class of drugs lower immunity and thus increases the risk of infection with COVID-19. It is also noted that adequate control of allergic diseases would indirectly reduce the risk of COVID-19 infection because patients are less likely to visit their physician.
The statement cites the Global Initiative for Asthma, which recommends continuation of all asthma therapies with the exception of nebulisers. This advice is based on the fact that during an acute attack, the use of a nebuliser increases the risk of disseminating COVID-19 to both other patients and health professionals. It is suggested that patients use metered-dose inhalers with a spacer if they suffer a severe attack.
5. Current knowledge might evolve and guidelines change
Recommendation five
Given that COVID-19 is rapidly spreading across the globe, the position paper recognises that an increasing number of people, including children with allergies are likely to become infected. Although there is currently no evidence to suggest that children with allergic airway diseases receiving AIT are at a higher risk of infection, new information may change this advice and allergists should remain flexible and keep abreast of any changes to recommendations.
6. Patients with immunodeficiency have an increased risk for infections with respiratory viruses
Recommendation six
Those who are immunodeficient are deemed to be in an at-risk category and are therefore advised to follow any national recommendations to reduce their risk of infection. In an effort to avoid disease exacerbations, patients should continue with their regular treatments and remain in contact with their allergy physician or team (via video or telemedicine) to ensure that any clinical symptoms can be quickly assessed and investigated.
The position paper suggests that clinical immunologists follow all advances in the science of COVID-19 as this may allow them to tailor their advice and treatment recommendations to patients in the near future.
Reference
Brough HA et al. Managing childhood allergies and immunodeficiencies during the respiratory virus epidemics – the 2020 COVID-19 pandemic. Pediatr Allergy Immunol 2020; Apr 22. doi: 10.1111/pai.13262. Online ahead of print.
A joint position statement from the European Academy of Allergy and Clinical Immunology (EAACI) and Allergic Rhinitis and its Impact on Asthma (ARIA) relating to the use of allergen-specific immunotherapy (AIT) has been published.
The position statement is designed to support allergists and any physicians performing AIT in their daily practice and provides clear recommendations for the use of these treatment in patients during the COVID-19 pandemic as discussed below.
AIT describes a disease-modifying therapy that provides a long-term clinical benefit in patients with immunoglobin E (IgE)-mediated, immediate-type allergic airways diseases such as allergic bronchial asthma and allergic rhinoconjuctivitis.
The objective of AIT is to decrease the symptoms experienced by a patient when exposed to a specific allergen and treatment typically involves gradual administration of increasing amounts of a specific allergen until a dose is reached at which immune tolerance is achieved.
AIT can also be used to reduce the risk of developing asthma in patients with allergic rhinitis and has been shown to be effective against IgE-mediated food allergies.
The joint position paper makes clear how the presence of allergic airway diseases are associated with an increased risk of infections but recognises that there is limited evidence of the impact of viral infections on allergic diseases.
Some evidence cited from studies of patients using AIT with influenza have demonstrated that there was no difference in symptoms in those with or without allergic asthma. Other work in patients with HIV has also shown that AIT treatment is both effective, safe and well-tolerated.
In an overview of the mode of action of AIT, the joint position statement discusses how allergen-specific immune tolerance is developed through several different mechanisms directed at T and B cells, leading to a suppression of their cytokines though this mechanism does not affect the whole immune system.
Consequently, patients using AIT are not likely to be become immunocompromised. The position paper however, does cite recent data that indicates how infection with COVID-19 leads to lymphopaenia and, in particular, a reduction in both CD4, CD8 and natural killer lymphocytes that affect a patient’s ability to mount an anti-viral response.
While AIT reduces allergen-specific Th2 cells, according to the available data, it appears that COVID-19 infection is linked to a systemic Th1 response and subsequent cytokine storm. These observations therefore suggest that AIT is unlikely to interfere with viral infections.
The position paper advises that allergy departments follow infection prevention and control measures introduced by the World Health Organization and the European Centre for Disease Prevention and Control, for all patients undergoing AIT as these measures cover the reporting and transfer of patients with possible or confirmed COVID-19 infection
In an effort to reduce the number of patients who may be infected coming into contact with allergy staff, it is suggested that those who feel ill with typical respiratory symptoms (for example, cough, fever) should contact their allergy department by telephone or via e-Health/telemedicine to seek medical advice and triage before attending their appointment.
A further recommendation is that all allergy service staff including doctors, nurses and administrative staff should:
The position paper advises that departments have access to appropriate personal protective equipment (PPE) to ensure standard, contact and droplet protection. It is also recommended that each allergy department appoints a dedicated member of staff who is able to take the lead on COVID-19 preparedness and to implement the relevant infrastructure and control measure policies.
A useful and practical suggestion in the position paper is for departments to create notices that are displayed on all entrance doors, listing the main COVID-19 symptoms. This is designed to ensure that visitors are aware of COVID-19 symptoms and informed that they should not enter the department if they have any of these recognised symptoms e.g. fever, cough.
In addition, everyone entering the department should adopt hand hygiene measures such as using soap and water or an alcohol-based hand rub.
The position paper advocates the use of a case-by-case approach for a risk assessment of whether individual staff undertaking AIT should use PPE.
Nevertheless, in light of the potential for airborne transmission of COVID-19, it is strongly advised that appropriate PPE is used, especially for aerosol-generating procedure such as swabbing. Another practice piece of advice that staff provide surgical masks for patients with respiratory symptoms.
AIT is available in several different formulations e.g. subcutaneous and sublingual and would normally require recurrent contact with a physician or nurse over extended periods time (which can be up to three years) before immune tolerance is developed.
This necessitates many patient appointments, especially among those receiving subcutaneous injections that are administered daily or weekly (during the up dosing phase) and monthly during the continuation phase.
In contrast, sublingual therapy although initiated at the allergy clinic can be continued by patients themselves at home thus avoiding the need to visit the department.
The position paper notes the recommendation to temporarily suspend both subcutaneous and sublingual therapies in patients who experience an acute respiratory tract infection until the infection has resolved and this recommendation is extended to those with COVID-19.
Therefore subcutaneous or sublingual AIT should be STOPPED in those with diagnosed or suspected COVID-19 infection.
However, AIT can be restarted or continued for patients who have recovered from COVID-19 and who are symptom free.
For patients who are not known or suspected of having COVID-19 infection:
Both subcutaneous and sublingual therapy should CONTINUE especially in life-threatening allergies such as venom allergy
The position statement concludes by stating that their recommendations are conditional due to the lack of available data on COVID-19 and that revisions will be implemented when any new or relevant information becomes available.
Reference
Akdis C et al. Handling of allergen immunotherapy in the COVID-19 pandemic: An ARIRA-EAACI statement. Allergy 2020; Apr 24 doi: 10.1111/all.14336. [Online ahead of print].
The question of whether or not to use face masks widely is important because, in the absence of a suitable pharmaceutical measure – be it vaccines to prevent or drugs to treat SARS-CoV-2 infection – non-pharmaceutical measures are currently the only means of controlling infection.
It has been suggested that the wearing of face masks might become the norm when the lockdown ends but before mass vaccination against SARS-CoV-2 can be implemented. The mayor of London, Sadiq Khan, has called for the wearing of ‘non-medical face masks’ in situations where social distancing is not possible. Trisha Greenhalgh, writing in the BMJ, argues that the use of face masks (type not specified) by the public is a sensible precaution.1 However, the evidence for the effectiveness of face masks in preventing infection is weak and in the UK there is concern that the use of medical masks would divert scarce supplies from front-line NHS and social care staff. Others have argued that the wearing of masks could create false sense of security and lead people to pay less attention to handwashing and social distancing.
Mask types
Several different types of masks are available:
For masks to be effective at preventing transmission of infection in non-healthcare settings we have to assume that the predominant mode of transmission is through inhalation of droplets resulting from coughs or sneezes. Masks could then work either by preventing release of droplets from infected persons and/or by preventing inhalation of droplets by uninfected persons.
Evidence
Two recent systematic reviews are of interest here. Xiao and colleagues2 found that trials of masks to reduce influenza infections were a mixed bag of trials that involved masking infected persons to prevent passing on infection, masking of uninfected people to prevent from becoming infected and general use of masks to reduce infection rates. Compliance was always an issue – masks don’t work if they are not worn – and many studies were small or underpowered. This review found no significant effect of face masks on transmission of laboratory-confirmed influenza.
Jefferson and colleagues (in the updated Cochrane review, preprint)3 concluded that masks alone had no significant effect in interrupting spread of influenza-like illness. They also made the point that further study is necessary and that benefits need to be balanced against harms. They noted that after the SARS epidemic in 2003, a large number of harms were identified including respiratory fatigue, poor work capability, increased nasal resistance, elevated levels of carbon dioxide, facial dermatitis, acne and potential self-contamination events. Although all the trials were conducted during outbreaks of seasonal influenza – a disease with similar modes of transmission to COVID-19 – they were undertaken during relatively low-transmission periods, and this limits generalisability to the COVID-19 situation.
Different approaches
If masks are in short supply then perhaps a different approach is needed, such as the use of re-usable masks. A number of institutions in the USA have looked at methods for sterilising N95 masks so that they can be re-used. For example, Duke University has established a method using hydrogen peroxide vapour – a standard technique for sterilisation in pharmaceutical isolators.
In Israel the Health Ministry has begun a project, in cooperation with textile experts, to produce high quality masks that are washable, re-usable and suitable for widespread public use. On the first day of operation, 300,000 masks were produced. Residents of areas where the infection rate is high will each receive a kit containing three masks and instructions for correct use.
A different approach has been adopted in Vietnam where all citizens are now required to wear masks. Disposable medical masks can be sterilised by microwaving at 800W for one minute if the masks are first moistened. Effectively this is steam sterilisation. This method is only suitable for standard disposable medical masks and cloth masks, other types of mask could contain components that are not suitable or safe for microwaving. Masks should be microwaved singly, preferably in a dedicated microwave oven (in hospitals and offices) rather than one that is also used for food.
Washable cloth masks were compared with surgical masks (in healthcare workers) in one study.4 This was a three-armed study that compared surgical masks, cloth masks, and ‘no-mask’ (control arm) The results showed that cloth masks were associated with significantly higher rates of influenza-like illness compared with the control (‘no mask’) arm. The authors concluded that cloth masks should not be recommended for health care workers. However, the control group followed ‘usual practice’ with regard to mask wearing. In fact only 1% of the control group wore ‘no mask’ (the majority wore cloth masks or a mixture of cloth and surgical masks. Thus the results do not tell us whether a cloth mask is better or worse than no mask.
In a recent addendum, the authors acknowledge that cloth masks used in the study could have become damp and contaminated during use. They therefore suggest that cloth masks, used a last resort, could be sprayed with sanitiser or subjected to UV disinfection during shift breaks. The cloth masks used were double-layer cotton fabric. Basic principles suggest that UV disinfection would be a poor option because UV light cannot disinfect what it cannot reach. This is one of the reasons why the Vietnamese authorities have recommended microwaving moistened disposable masks at 800W for one minute instead.
DIY masks
If the use of non-medical face masks by the public in the UK is recommended, there could be a proliferation of DIY masks. It may be useful to know that the Centers for Disease Control (CDC) has produced detailed guidance on cloth face coverings including instructions for sewn and ‘no-sew’ face protection masks. 5 Another emergency approach comes from the French Medicine Academy, which has instructions on how to make a disposable mask using a paper napkin, two elastic bands and a stapler.6
Those interested in the particle filtration efficiency of cloth masks will be interested to see a pre-print that shows how adding a layer of nylon stocking (or tights) can improve the filtration efficiency of a mask.7
Konda and colleagues provide a more detailed discussion of the mechanics of masks and note that gaps resulting from an improper fit of the mask can result in over a 60% decrease in the filtration efficiency.8
Bottom lines
References
28th April 2020
The researchers found a diverse collection mutations in a series of isolates from 11 infected patients during the early stages of the outbreak in Wuhan city.
Interestingly, 5 of these 11 patients either worked in or travelled to Wuhan before they were diagnosed which suggests that the patients were either first or second-generation viral victims. Apart from one patient, the others had moderate or severe symptoms but fortunately all survived.
In total, 9 of the 31 mutations identified were novel, despite the fact that the samples were collected early in the pandemic which suggested that the diversity of the viral strains was underappreciated. Furthermore, six of these mutations were in the spike glycoprotein (S protein) which allows the virus to gain entry in host cells. To assess the impact of these mutations, the authors undertook an in vitro infectivity assay and found significant variation in viral load and that viral load correlated with a higher level of cell death.
It was concluded that the current mutations occurring in COVID-19 have the functional potential to impact on viral load pathogenicity, making an effective vaccine much more difficult.
Reference
Yoa H et al. Patient-derived mutations impact pathogenicity of SARS-CoV-2. MedRxiv https://doi.org/10.1101/2020.04.14.20060160
However, a recent meta-analysis has provided a quantitative assessment of the risks of various comorbidities among those infected with COVID-19. Researchers undertook a literature review up to 1 March 2020 which identified six studies including 1558 patients with COVID-19, of which 324 (20.8%) were severe and the risk of disease progression was expressed in terms of the odds ratio (OR).
The results indicated that patients with COPD had a 5.9-fold higher risk (OR = 5.97) of disease progression compared to those without the condition. There was a lower but still significant risk of disease aggravation in patients with cardiovascular disease (OR = 2.93), diabetes (OR = 2.47) and hypertension (OR = 2.29).
In contrast, there did not appear to be a correlation between liver or kidney disease and malignant tumours. A noted limitation of the data was the small sample size and the fact that many patients had more than one co-morbidity which may indicate that the risks were under-estimated.
Nevertheless, these data are of value in the development of strategies to minimise the risks for these patient groups.
Reference
Wang B et al. Does comorbidity increase the risk of patients with COVID-19: evidence from meta-analysis. Aging 2020;12(7):6049-57.
Initially, 20,000 households will be contacted for testing although the aim is to recruit a representative sample (by age and geography) of up to 300,00 people over the next 12 months to provide a better understanding of the current community infection rate and to determine how many people have developed antibodies to the virus.
Irrespective of whether patients report COVID-19 symptoms, all household members will be asked to provide anonymised samples from self-administered nasal and throats swabs to determine whether they have the virus. The swabbing will be repeated weekly (for the first five weeks) and then monthly over the next 12 months. Around 1000 adults will also have monthly blood samples taken at home (by a trained healthcare worker) for the next 12 months to test for COVID-19 antibodies, unless a household member has COVID-19 symptoms or is self-isolating or shielding.
The study is the fourth pillar of the UK government’s testing strategy, and it is anticipated that the results will enable researchers to predict the future trajectory of infection and inform on the most appropriate next steps.
Further information can be found that the DHSC website.
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