Rapid response

Preventing viral transmissions in communities and households: strategies from a multidisciplinary view highly needed

Re: Reduction of secondary transmission of SARS-COV-2 in households by facemask use, disinfection and social distancing: a cohort study in Beijing, China. Yu Wang. BMJ Global Health 2020; 5: e002794, doi: 10.1136/bmjgh-2020-002794

Dear Editor,

In their original research in BMJ Global Health Wang et al. (1) claim that their study provides the first evidence for the effectiveness of face mask use and social distancing in preventing COVID-19 transmission, not just in public spaces but inside the household with members at risk of getting infected. They argue that these non-pharmaceutical interventions (NPI) reduce risk for families living with someone in quarantine or isolation and families of healthcare workers who may face ongoing risk and that NPI are effective at preventing transmission even in homes that are crowded and small.

More specific, Wang et al. (1) conclude that face mask use 2 days prior to symptom onset could be preventing secondary transmission while starting to wear facemasks after the onset of symptoms did not have any effect on a secondary transmission. Almost a quarter of family members became infected in the families with a second transmission ( total of 77 persons with 13 children with a mean age of 3 years with mild symptoms and one child with asymptomatic symptoms, 64 adult cases; 3 asymptomatic, 53 with mild symptoms, 7 severe cases and 1 critical case ). The median size of the families participating in this retrospective cohort study was 4 (ranging from 2 to 9 usually with children, parents and grandparents).

The conclusion and advices in the article based on data and design of the study presented needs more evidence. A retrospective cohort study based on questionnaires via telephone interviews is highly sensitive to bias and confounding. Several aspects that can influence viral infections and transmission in households have not been discussed, neither the negative aspects of implementing NPI in households and universal facemask wearing are discussed.
In this rapid response we briefly explain our interpretation of the data presented and the impact of universal face masking, social distancing and NPI as a preventive strategy in viral transmissions in households.

1. Unfortunately, the study does not explain why 39 households met exclusion criteria in the 128 households without secondary transmission compared to only 1 household in the 49 households with secondary transmission.
2. The authors do not discuss a higher percentage of people with co-morbidities in the households with secondary transmission (Table 1). Or whether severe and critical cases in the second transmission were people suffering from co-morbidities wearing masks prior to showing symptoms and/or the primary case was wearing a facemask all day or sometimes 2 days before the onset of symptoms. In many scientific publications and media articles a relation of developing severe COVID-19, Acute Respiratory Distress Syndrome (ARDS) for people with overweight, diabetes, cardiovascular disease and elderly, frail people has been described. As well as a disproportionate burden on black, Asian and minority ethnic individuals and communities.
3. In Table 2 a delay in laboratory confirmation in the group of people with secondary transmission as compared to the group of families without secondary transmission is observed. Previously, it has been reported that there have been difficulties with RT PCR tests at some stages of the epidemic in China (2). It is not clear if people have been repeatedly tested for the presence of SARS-COV-2 virus to confirm infection with the virus. The article states that the virus in respiratory or blood specimen was ‘highly homologous’ with known SARS-COV-2 through gene sequencing. It is not clear if this could be SARS-COV-1 or one of the other beta coronavirus frequently causing respiratory infections during winter times.
4. Table 3 shows a major difference in the ventilation duration per day which was less in frequency and total hours per day and residential area per capita in the group of families with secondary transmission. The review of prof Moriyama et al. “Seasonality of respiratory viral infections” indicate that the winter environment promotes the spread of a variety of respiratory virus infections. In the industrialized world most people interact and spend 90 % of their lifetime in enclosed spaces and share a limited amount of breathing air. The implication is that indoor climate and air change rates, modulated by outdoor seasonal conditions are the key drivers of seasonal patterns in epidemiology. In addition, exposure to outdoor conditions (albeit 10 % of lifetime) contributes to alteration of respiratory defence of the existing virome (3). The possibility that dry and unventilated air can increase opportunity to spread influenza virus infection in winter times has been demonstrated in mice studies. The inhalation of dry air causes immediate effects by epithelial cilia loss, impaired epithelial cell repair in lungs and inflammation of the trachea in a study with guinea pigs. Ventilation to refresh the air in crowded homes to remove aerosols with virions and support an effective immune system is important. Furthermore, recent studies reveal that season dependent environmental factors, such as temperature and humidity can affect the host antiviral innate immunity against respiratory infections (3). Therefore, it cannot be excluded that a simple ventilation of the home could have been of influence in the second transmission in the group of families with second transmissions.
5. Table 1 describes that various facemasks (cloth masks, medical masks or N95 masks) were used. How frequently masks were refreshed or washed, taken of, re-used and disposed in an appropriate way is not documented. The quality of facemasks can differ in pore size and materials used. Depending on the materials used toxic material or fibres may impair the innate immune system. A study of Chughtai et al demonstrated the existence of respiratory pathogens on the outer surface of used medical masks which may result in self-contamination. The risk was higher with longer duration of mask use (> 6h) and with higher rates of clinical contact (4). Furthermore, heart rate, microclimate temperature humidity and subjective ratings were significantly influenced by wearing of different kinds of facemasks. The local thermal stimulus also affected heat exchange from the respiratory tract. Microclimate temperature, humidity and skin temperature inside the facemask increased with the start of step exercise, which led to different perceptions of humidity, heat and high breathing resistance among subjects wearing facemasks. High breathing resistance makes it difficult for the subject to breathe and take in sufficient oxygen. Shortage of oxygen stimulates the sympathetic nervous system and increase heart rate and may results in stress and anxiety experience (5). It is probable that people feel unfit, fatigued and overall discomfort due to this reason. For people and children with hearing loss face masks can be devastating (6).
If facemasks determine a humid habitat where the SARS-COV-2 virus can remain active due to the water vapour continuously provided by breathing and captured by the mask fabric , they determine an increase in viral load and therefore they can defeat of the innate immunity and increase in infections. Whereas the main purpose of the innate immune system is to prevent the spread and movement of pathogens through the body. Other important potential side effects of wearing face masks that we should bear in mind have been clearly described by dr AL Lazzarino on 20 April 2020 in a rapid response to the article of Greenlagh et al; Face masks for the public during covid-19 crisis(7)
In the Advice on the use of masks in the context of COVID-19, interim guidance 5 June 2020 the WHO writes that potential harms and risks should be carefully taken into account when adopting the approach of targeted continuous medical mask use including self-contamination, dermatitis, false security, uncomfortable to wear, risk for droplet transmission, difficulty wearing in hot and humid environments and by vulnerable populations with mental health disorders, developmental disabilities, the deaf and hard of hearing community and children (8).
6. The negative influence of stress and anxiety on the immune system increasing the risk of upper respiratory tract infections has been well documented (9). In the period February – March China was in lockdown and families with people infected with COVID-19 virus were in quarantine. Symptoms of Post-Traumatic Stress Disorder (PTSD) and depression were observed in 28,9 % and 31,2 % of respondents in the study, respectively. has been described in Toronto after a period of quarantine during the SARS epidemic in 2002 (10). Longer durations of quarantine was associated with an increased prevalence of PTSD symptoms. Acquaintance with or direct exposure to someone with a diagnosis of SARS was also associated with PTSD and depressive symptoms.
7. Another major impact on the effectiveness of the immune system is nutrition and lifestyle. It is not clear if persons included in the study started to eat differently due to stress, more sitting hours in a crowded home and if families had less possibilities to buy fresh food i.e. unprocessed vegetables, fruit and meat. There could have been a difference between the group of families without transmission and families with a secondary transmission. The role of nutrition and lifestyle (sleep, social interaction and being active outdoors) in view of the preparedness for a second peak of COVID-19 for all people especially for those at higher risk preventing severe viral infections by reversing weight loss, diabetes type 2 and other chronic diseases was published by Fiona Godlee : editor in chief of the BMJ (11).
8. In the perspective on Universal Masking in Hospitals in the Covid-19 era American doctors wrote in the New England Journal of Medicine “We know that wearing a mask outside healthcare facilities, offers little, if any protection from infection. Public health authorities define a significant exposure to Covid-19 as face to face contact within 6 feet with a patient with symptomatic Covid-19 that is sustained for at least a few minutes (and some say more than 10 minutes or even 30 minutes). The chance of catching Covid-19 from passing interaction in a public space is therefore minimal. In many cases, the desire for widespread masking is a reflective reaction to anxiety over the pandemic. Focusing on universal masking alone may paradoxically lead to more transmission of Covid-19 if it diverts attention from more fundamental infection-control measures”
Results from cluster randomized controlled trials on the use of masks among young adults living in university residences in the United States of America indicate that face masks may reduce the rate of influenza-like illness but showed no impact on risk of laboratory confirmed influenza. At present there is no direct evidence (from studies on COVID-19 and in healthy people in the community) on the effectiveness of universal masking of healthy people in the community to prevent infection with respiratory viruses, including COVID-19 (12)

Advice on universal face mask use and other NPI in households for people at risk or during epidemics for persons of a family of whom one or more are working in healthcare needs more advanced studies. Not only is the evidential basis insufficient, also potential risks argue against the implementation of mask wearing by billions of people and healthcare workers in family circumstances. A review of available scientific publications evaluating on the efficacy in limiting viral transmission and the impact on the physiology, immunity, mental, social, ecological (environmental) and economic level will be highly valuable for defining strategies to prevent future viral infections and transmissions. Especially in the presence of young children, people with mental disorders and disabilities and elderly people in households the negative impact on physiology, immunity as well as psychology with limitations in verbal and nonverbal expression and a risk of developing a Post-Traumatic Stress Syndrome due to quarantine needs more attention. Simple ventilation and sufficient air humidity % instructions in households, offices, transport, public areas and healthcare settings might be more effective in limiting viral transmission and entail less negative effects on physiology, immunological, social and mental level. At the mental-psychological level, face masks interfere with the exchange of facial expressions, which is quintessential for mental health. Research on mirror neurons (13) showed that humans constantly mirror each other’s facial expressions and that this exchange is the neural basis of empathy, in this respect that it allows to gauge the affective and emotional state of the other. In particular within the mother-child relationship, the quality of the affective exchange is directly related to overall mental and physical health, to this extent that when quality is poor, mortality rates in children raise dramatically (14). This has been confirmed in the most straightforward way in the field of psycho-neuro-immunology, remarkably enough specifically in viral lung disease. In 2008, Nielsen and his colleagues (15) found in a naturalistic study that mental stress leads to significantly higher mortality rates in humans suffering from viral lung disease; in 2020, Wieduwild et al.(16) reported that mice are 40% more likely to die from viral infections due to experimentally generated stress.
Moreover, with higher temperatures, sunlight and high humidity in countries in the Northern hemisphere the number of people dying from Covid-19 have been drastically reduced in the past two months. We need to use the summertime effectively to repair and boost the immune system and develop a humoral and cellular immunity to the SARS-COV-2 virus developing herd immunity among the population by being outdoors, social interactions and exposure to sunlight. At the same time improve the ventilation and absolute humidity in healthcare settings and support the immune system by improving the vitamin status of elderly people and people with co-morbidities at risk for viral infections.

References
1. Wang Y, Tian H, Zhang L, Zhang M, Guo D, Wu W et al. Reduction of secondary transmission of SARS-COV-2 in households by face mask use, disinfection and social distancing: a short study in Beijing China. BMJ Global Health 2020; 5: e002794, doi: 10.1136/bmjgh-2020-002794
2. Li Y, Yar L, Li J, Chen L, Sang Y, Cai Z, Yang C. Stability issues on RT-PCR Testing of SARS-COV-2 for hospitalized patients clinically diagnosed with COVID19. J. Med. Virol. 2020; 92:903-908. Doi: 10.1002/jmv/25768.
3. Moriyama M, Hugentobler WJ, Iwasaki I. Seasonality of respiratory viral infections. Annual reviews of virology. 2020 7: 2.1-2.19 doi: 10.1146/annurev-virology-012420-02445
4. Chughtai AA, Stelzer-braid S, Rawlinson W, Potivivio G, Wang Q, Pan Y et al. Contamination by respiratory viruses on the outer surface of medical masks used by hospital healthcare workers. BMC Infect. Dis. 2019: 19:491. Doi:1186/s12879-019-4109-x
5. Liu Y, Tokura H, Guo YP, Wong ASW, Wong T, Chung J and Newton E. Effects of wearing N95 and surgical facemasks on heart rate, thermal stress and subjective sensations. Int Arch Occup Environ Health 2005; 78(5): 501-509. Doi 10.1007/s00420-004-0584-4
6. Chodosh J, Freedman ML, Weinstein BE, Blustein J. Face masks can be devastating for people with hearing loss BMJ 2020: 370 doi: /10.1136/bmj.m2683
7. Greenlagh T, Schmid MB. Czypionka T, Bassler D, Gruer L. Face masks for the public during the covid-19 crisis. BMJ 2020:369:m1435 doi:10.1136bmj.m1435. Rapid response Covid-19: important potential side effects of wearing face masks that we should bear in mind. Lazzarino AL. 20 April 2020.
8. Advice on the use of masks in the context of COVID-19. Interim guidance. 5 June 2020. https//www.who.int/publications-detail/global-surveillance-for-covid-19 caused-by-human-infection-with-covid19-virus-interim-guidance
9. Drummond PD, Hewson-Brower B. Increased psychosocial stress and decreased mucosal immunity in children with recurrent upper respiratory tract infections. J. Psych. Res. 1997.43(3):271-278. Doi:10.1016/S0022-3999(97)00002-0
10. Hawryluck L, Gold WL, Robinson S, Pogorski S, Gales S Styra R. SARS Control and Psychological effects of quarantine. Emerg. Infect. Dis. 2004. 10(7): 1206-1212. Doi: 10.3201/eid1007.030703
11. Godlee F. Covid-19: What we eat matters all the more now. BMJ 2020;370:n2840. Doi.org/10136/bmjm2840
12. Klompas M, Morris CA, Sinclair J, Pearson M, Shenoy ES et al. Universal masking in Hospitals in the Covid-19 era. New England Journal of Medicine. 2020; 382:e63 doi: 10.1056/NEJMp2006372
13. Rizolatti G, Craighero L. The mirror neuron system. Annu Rev Neurosci 2004; 27:169-192. Doi: 10.1146/annurev.neuro.27.070203.144230
14. Spitz, R. A. (1965). The first year of life: a psychoanalytic study of normal and deviant development of object relations. New York: International Universities Press.
15. Nielsen N, Kristensen T, Schnohr P, Gronbaek M. Perceived stress and cause-specific mortality among men and women: results from a prospective cohort study. Am J Epid 2008; 168(5); 481-491. https://doi.org/10.1093/aje/kwn154
16. Wieduwild E., Girard-Madoux JM, Quatrini , Laprie C, Chasson L, Rossignol R, Bernat C, Guia S, Ugolini S. 2-adrenergic signas downregulate the innate immune response and reduce host resistance to viral infection. J Exp Med 2020; 217(4). e20190554. Doi.org/10.1084/jem.20190554

Competing interests: none

Dr Carla Peeters
CEO COBALA Good Care Feels Better®
Immunology, nutrition and health transformation expert
Utrecht, The Netherlands
Professor Dr Mattias Desmet
Faculty of Psychology and Educational Sciences
University Ghent
Ghent, Belgium

The COVID-19 pandemic has taken the world by storm, Low- and Middle- Income Countries (LMICs) not withstanding. Cabore et al modelled best estimates for peak prevalence of the virus on the African continent to be projected at more than 37 million symptomatic cases, requiring 4.6 million hospitaliations. Current estimates by Africa CDC show over 1 million cases as of August 6th, 2020, and more than 22,000 deaths [1]. South Africa has the highest prevalence with more than half a million reported cases, followed by Egypt and Nigeria, respectively. While the actual incidence and mortality rates may be evasive given limited access to testing globally [2], it is clear that the disease has not been forgiving on African soil either.

Non-Communicable Diseases (NCDs) constitute the backdrop for worse outcomes among those infected with COVID-19 [3], and those with poorer access to care fare worse. While NCDs have gained increasing attention in the last decade, the current pandemic illuminates the alarming gap in data on the double burden of disease that is threatened by a continued lag in focus on NCDs – an improved understanding of which would have been critical in effectively addressing our current plight.

A prime example of this is in the case of research addressing NCDs in the emergency care setting, an area of research in global health that is virtually non-existent in many resource-variable settings like Kenya, which has the highest number of COVID-19 cases in Eastern Africa. As with any pandemic, emergency care acts as the receptacle for patients in extremis, with severe cases of illness, including those with imminent oxygen needs and breathing support with COVID-19 - two needs highlighted by Cabore et al. This has occurred with COVID-19 [4], as in other public health crises before it. The spotlight on emergency care as a priority for government agendas globally in the 2019 WHA 72.16 [5] resolution was a step in the right direction for the progress needed in countries where neglect of emergency care infrastructure has been appalling, and even fatal. Further research on best practices for emergency care in LMICs, including responsiveness in crises, understanding burden of NCDs in the emergency care setting, and the effect of the double burden in populations seeking care there cannot be overstated. To that end, our recent study in the largest public emergency department in East Africa [6] called Kenyatta National Hospital, shows equal or worse outcomes for all NCDs and leading risk factors outlined by the WHO’s 2013 action plan [7]. All the same, the capacity to handle emergency cases in Kenya, like most African nations, remains dismal at best due to lack of prioritization: lack of basic resources like oxygen, lack of adequately trained emergency professionals, and lack of health system infrastructure that facilitates timely access for patients.

For the first time, the global health community may have realized the crux of emergency care: as the front-lines to our healthcare systems. Communicable disease pandemics, and NCD co-afflictions alike. The WHO’s emergency care office is home to many initiatives that advance this agenda. I would hope that the remainder of the global health community follows suit.

1. Coronavirus Disease 2019 (COVID-19): Africa CDC Dashboard. 2020; Available from: https://africacdc.org/covid-19/.
2. World Health Organization. (‎2020)‎. Laboratory testing strategy recommendations for COVID-19: interim guidance, 21 March 2020. World Health Organization. https://apps.who.int/iris/handle/10665/331509. License: CC BY-NC-SA 3.0 IGO.
3. Yang, J., et al., Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Int J Infect Dis, 2020. 94: p. 91-95.
4. Giving Oxygen to COVID-19 Patients in Kenya. 2020 August 8th, 2020]; Available from: https://www.emergencymedicinekenya.org/oxygenmanifold/.
5. World Health Assembly, Resolution 72.16. Emergency Care Systems for Universal Health Coverage: Ensuring Timely Care for the Acutely Ill and Injured. 2019.
6. Ngaruiya, M., MSc, DTMH, Christine, et al., The last frontier for global Non-Communicable Disease action: the Emergency Department - a cross-sectional study from East Africa. medRxiv, 2020: p. 2020.07.29.20164632.
7. World Health Organization. WHO global action plan: for the prevention and control of noncommunicable diseases 2013-2020. 2013; Available from: http://apps.who.int/iris/bitstream/10665/94384/1/9789241506236_eng.pdf.

Dear Editor,

It is with great interest that I read the original research by Lobkowicz et al, ascertaining that coinfections do not strongly influence clinical manifestations of uncomplicated ZIKV infections [1]. With this interesting finding in mind, it is important to remember that Neglected Tropical Diseases (NTDs) exist and persist for social and economic reasons that enable the vectors and pathogens to take advantage of changes in the behavioural and physical environment [2]. More than 70% of countries and territories affected by NTDs are low-income and low and middle income countries [2]. Thus, there are extreme inequalities with regards to disease distribution. People are affected by NTDs because of an array of social determinants. It is plausible that these social determinants may allow for coinfections of Zika (ZIKV), dengue virus (DENV) and chikungunya (CHIKV).

Social Determinants of Health (SDH) are the conditions in which individuals are born, grow, work, live and age, and the wider set of forces and systems shaping the conditions of daily life [3]. SDH encompass socioeconomic factors, environmental factors and biological factors. These factors play a fundamental role in the proliferation of vector-borne diseases such as ZIKV, DENV and CHIKV. The relationship between the vector and SDH is complex, yet it is extremely important to recognise in order to evaluate the impact of socioeconomic factors on infectious diseases.

There are major inequalities with regards to disease distribution. The relationship between Gross Domestic Product (GDP) and health is a starting point for examination of inequalities in the global health context. High income countries tend to have greater GDPs, which often means nations have better health systems and social services.

The distribution of ZIKV infection is unevenly spread across the globe [2]. The weight of Zika Virus Disease falls on the poor for different reasons. In tropical urban areas, those from a low socioeconomic income group are not able to manage the cost of air-conditioning, window screens, or insect repellent [4]. With no piped water and poor sanitation, they are compelled to store water in containers, giving perfect conditions to the expansion of mosquitoes [5].

The combination of ZIKV, DENV and CHIKV coinfections obfuscates the public health problem in various populations where complications due to poverty, poor basic sanitation and poor vector control persist. Further work is needed to elucidate the importance of the interactions between socio-environmental factors and transmission of ZIKV, DENV and CHIKV. The importance of SDH when understanding the risk factors that potentiate NTDs spread, is crucial for public health academics, health ministers and governments, as any interventions must consider ecological, biological and social factors.

References

1. Lobkowicz L, Ramond A, Sanchez Clemente N, et al. The frequency and clinical presentation of Zika virus coinfections: a systematic review. BMJ Global Health 2020;5:e002350.

2. Manderson L, Aagaard-Hansen J, Allotey P, Gyapong M, Sommerfeld J. Social Research on Neglected Diseases of Poverty: Continuing and Emerging Themes. PLoS Neglected Tropical Diseases. 2009;3(2):e332.

3. WHO. Social determinants of health [Internet]. World Health Organization. 2020 [cited 10 May 2020]. Available from: https://www.who.int/social_determinants/en/

4. Lundgren K, Kjellstrom T. Sustainability Challenges from Climate Change and Air Conditioning Use in Urban Areas. Sustainability. 2013;5(7):3116-3128.

5. Dhimal M, Gautam I, Joshi H, O’Hara R, Ahrens B, Kuch U. Risk Factors for the Presence of Chikungunya and Dengue Vectors (Aedes aegypti and Aedes albopictus), Their Altitudinal Distribution and Climatic Determinants of Their Abundance in Central Nepal. PLOS Neglected Tropical Diseases. 2015;9(3):e0003545.