This article was written by Caroline Tang and was first published by UNSW Newsroom. It is reproduced here with their kind permission.

Two UNSW Sydney academics discuss how coronavirus – primarily a respiratory virus – affects smokers. 

Professor Christine Jenkins, AM, is Conjoint Professor of Respiratory Medicine at UNSW Sydney, Head of the Respiratory Group at The George institute for Global Health and Chair of the Lung Foundation Australia. She has led many clinical trials in airways disease and held major roles in advocacy and leadership for lung health in Australia.

Associate Professor Freddy Sitas is the Director of the Centre for Primary Care and Equity at UNSW Sydney and Conjoint Professor at the UNSW School of Public Health and Community Medicine. A/Prof Sitas has more than 20 years’ experience researching smoking-related hospitalisations, cancers and deaths, including working with the World Health Organization and Clinical Oncology Society of Australia on smoking cessation.

Are smokers more susceptible to catching COVID-19?

Professor Jenkins said we don’t know for certain.

“But on the basis of information we have about the nature of chronic lung disease, we know that when you have lung inflammation present already, you are more likely to be prone to invasion and severe damage from other causes of lung inflammation. Smokers may also be more vulnerable through bringing their hands to their mouths and inhaling repeatedly,” Prof Jenkins said.

“We are waiting to see the data, however, that convincingly tells us that people with chronic lung disease – which many smokers suffer from – are more vulnerable to picking up COVID-19.”

Associate Professor Sitas said there was a lot of peer-reviewed literature on the mechanism of how smoking harmed cells in the lungs and how that made smokers more susceptible to infectious respiratory diseases, such as influenza, pneumonia and tuberculosis.

“This has been summarised by Cancer Council Victoria: the harm that smoking causes to the lungs includes: mild immune impairment and significant impaired function of cilia in the lung. Cilia have the vital role of clearing foreign bodies in the lungs; i.e., viruses and bacteria,” A/Prof Sitas said.

“So, smokers get more respiratory infections, and colds of greater severity than non-smokers. This includes respiratory syncytial viruses, which cause infections of the lungs and respiratory tract. Their rate of transmission is greater in smokers than in non-smokers.”

Will smokers have a worse outcome if they catch COVID-19?

Professor Jenkins said we did not know yet if smokers were more vulnerable to serious consequences if they acquired COVID-19, but there were very specific reasons why people with chronic lung disease could be badly affected by COVID-19.

“These reasons are not all about increased susceptibility to catching the virus: some of them are about increased susceptibility to catastrophic outcomes because these people already have lung damage,” Prof Jenkins said.

“We would expect smokers to be at greater risk of lung injury from a nasty respiratory virus and I don't have any reason to think COVID-19 is different. But we are, as yet, not fully informed about this and the published papers, as yet don't identify smokers as being more at risk than non-smokers. However, I say that with a lot of reservation about what we're seeing in the data.

“The only available evidence specifically addressing risk for people with chronic lung disease comes from early cases published by the Chinese Center for Disease Control and Prevention (China CDC), which suggests that amongst co-existing disorders as COVID-19 risk factors, hypertension and diabetes were stronger predictive factors for a poor outcome from COVID-19 than Chronic Obstructive Pulmonary Disease (COPD).

“From everything we know about the effect of viral respiratory infections, people with COPD are very much more likely to be predisposed to bad outcomes from COVID-19. COPD is a disease that smokers get, as well as people working in dusty environments and women in developing countries who are particularly exposed to biomass fuels in heating and cooking, such as animal dung. So, we are greatly concerned about what will happen when COVID-19 reaches communities that have very, very poor health infrastructure. Genetic causes of COPD are rare.

“So, people with COPD who have moderate to severe disease can have very abnormal oxygen levels day-by-day and they manage. But the moment there’s an additional problem that causes a further loss of ability to transfer oxygen from the air into the bloodstream, then they are at profound risk of deterioration.”

Associate Professor Sitas said for smokers, there were a number of “strands” of convincing evidence that suggested smokers would have worse outcomes if they caught COVID-19. 

“Risks of dying from other known infectious respiratory diseases in smokers are 50 per cent to 300 per cent higher than in non-smokers. We have been underestimating the role of infectious lung disease deaths caused by smoking,” A/Prof Sitas said.

“For example, in South Africa it was only when we added a question about smoking on death certificates that we discovered tuberculosis was the leading cause of death caused by smoking in black South Africans. The COVID-19 pandemic is evolving but a breakdown of sex ratios shows that males (who smoke more in China, Iran and Italy), are more at risk of dying from COVID-19 than females.

“Aside from the sex ratios, there is a Chinese Medical Journal report from Wuhan on 78 cases showing those who have more serious respiratory outcomes were nine times more likely to be smokers. We already know that people with pre-existing health conditions fare worse from COVID-19. These studies are not perfect but it’s simple logic to infer that smokers will do worse than non-smokers.

“There is a good opinion piece published in The BMJ Opinion about COVID-19 and quitting smoking during respiratory virus epidemics, while the United Kingdom’s Secretary of State for Health has urged smokers to quit based on research on previous coronaviruses that showed smoking made the impact of a coronavirus worse.

“This is a good opportunity for smokers who are in a high-risk group of catching COVID-19, or who are living with a person who is at high risk, to seriously consider quitting.

“The scientific evidence for causality is evolving and is overall positive. We have evidence from mechanistic studies, examples from other respiratory diseases, emerging epidemiological data, and plain common sense that smoking may turn out to play a more serious role in COVID-19 deaths than previously anticipated.”

Recent claims linking hypertension treatments to COVID-19 led to a series of statements being issued by medical societies, including the International Society for Hypertension, cautioning against an overreaction.

We asked Professor Alta Schutte, President of the International Society of Hypertension (ISH), and Professorial Fellow, Cardiovascular Program at the George Institute, what it was all about.

How did it start?

Correspondence published in the prestigious Lancet Respiratory Medicine journal suggested that the most commonly used medications to treat high blood pressure - ACE inhibitors and angiotensin receptor blockers – may increase the risk for infection in patients with hypertension and diabetes mellitus, and may also increase the risk for severe and fatal COVID-19.

Amplified by social media and the mass circulation of inaccurate medical information, this idea led to confusion among healthcare professionals and some patients not taking their medication.

What was the basis for it?

The issue surrounding ACE-inhibitors and ARBs stems from the fact the COVID-19 virus binds to a particular protein on the cell surface – this is how it enters cells. What we know from inconsistent animal studies is that ARBs and ACE-inhibitors may increase the production of this protein in the body as many as three to five times. It’s a hypothesis for which there is a good logic, but it has not been proven in humans.

Why was it important for ISH to put out a statement on this?

The consequences of stopping taking ARBs or ACE inhibitors is that blood pressure can get out of control and this can lead to heart attacks and strokes. There is a much greater risk for these cardiovascular events than for getting infected with COVID-19.

Discontinuing treatment with these medications could cause a great deal of harm, particularly in these times where healthcare systems are already stretched.

So what do we know about the risk of COVID-19 infection in people with hypertension?

To date - there is no evidence that people with hypertension are over-represented amongst those seriously infected by COVID-19. Many challenge this statement as recent scientific reports from COVID-19 populations often suggest that hypertension was common in those with COVID-19 infection. It is important to point out that for all of these reports, no one accounted for the age of the populations. We know that people over the age of 60 have a >90%  lifetime risk to develop hypertension, and thus age (not hypertension) may be the main reason for infection.

What about the proposed association between hypertension treatments and worse outcomes from COVID-19?

There are no clinical data in humans to show that ACE-Inhibitors or ARBs either improve or worsen susceptibility to COVID-19 infection nor do they affect the outcomes of those infected. Important to note that there are also animal studies suggesting that the use of ACE-inhibitors or ARB could be protective in the setting of COVID-19 infection. But again no data is available in humans.

What’s your advice?

In the absence of any such compelling data the ISH strongly recommend that the routine use of ACE-Inhibitors or ARBs to treat raised blood pressure should continue and should not be influenced by concerns about COVID-19 infection.

Do you think this will change?

It is possible that in light of new clinical trial data in humans it may be that the management of raised blood pressure could be modified to reduce susceptibility to or improve outcomes among those infected by COVID-19. However, currently no such data are available to make such recommendations, and so no changes should be made.

Senior Project Manager with The George Institute India Balaji Gummidi describes the joint efforts of the STOP CKDu team to ensure dialysis patients in Andhra Pradesh continue to receive their life-saving treatment during the COVID-19 lockdown.

Like the rest of India, the people of Andhra Pradesh are in a complete lockdown for 21 days to fight the coronavirus pandemic. This lockdown presents a number of challenges to patients who need to undergo regular dialysis.  On the very second day of the lockdown, dialysis patients in Srikakulam district were in for a shock – they were under strict orders not to leave their homes and also had no means of transport to reach their respective centres.    

As dialysis is a life-saver and is needed to stay healthy and alive, the affected people realised it cannot be postponed.  They cannot stay in lockdown or be quarantined effectively and needed to visit the dialysis centres for a four-hour session at least two to three times a week. These included people who live far from the centres and therefore need to have some means of transport to reach dialysis units. Not having dialysis meant certain death and so, staying at home for fear of getting coronavirus was not an option.

Immediately, what came to their mind is the helpline number of the Kidney Research Innovation and Patient Assistance Centre (KRIPA), which the Andhra Pradesh Government established with technical support from The George Institute India at Palasa, Srikakulam District. On the morning of the second day of the lockdown, staff at the KRIPA centre started getting questions from patients on the helpline number regarding the need to continue their dialysis sessions and how they could reach the centre.

Ramana Rao, a 48-year resident of Akkupalli village, used the hotline to say that dialysis was scheduled for him on that day and he was not able to find transport to reach the centre at RIMS Srikakulam. K Aruna, a 35-year-old mother of two from Gollamakaranapalli village, was desperate to attend her dialysis session at Palasa community health centre but did not know what to do.

A total of 369 patients are registered at these centres and under the Andhra Pradesh Government’s YSR Arogyosri scheme dialysis is being provided free of cost. There are three dialysis units in the region that conduct around 230 sessions per day. The STOP CKDu project team at The George Institute India has been with working in these villages for the last year and a half, conducting awareness activities and research to understand the burden of kidney disease in the area. All team members knew how important it was that something was done quickly.

Both staff and patients understood that skipping dialysis can lead to serious adverse effects. Nevertheless, with the strict travel restrictions in place and closure of public and private transport, they were at a loss to understand how to get to the dialysis centres. They had already heard that six patients had missed their sessions. 

STOP CKDu team members swung into action – they knew that there are two referral vans and one mini ambulance for all four community health centres in the region. The district health authorities were contacted and with direct orders from the district collector of Srikakulam, the vehicles were commissioned to transport these desperate patients to the dialysis centres.

The team ensured that the vehicles were fully sanitised, and the driver was trained to follow safety measures. Led by K Tirupathi, counsellor of KRIPA centre, the STOP CKDu team is monitoring the logistics and scheduling the pick-up and drop off of people in need of getting this life-saving treatment. Around 30 to 35 patients are utilising these services daily.

It is turning out to be a life-saving intervention for these people.

Dr Holger Möeller is an epidemiologist in the injury division at The George Institute for Global Health, Australia, with expertise in injury epidemiology and the analysis of longitudinal linked health data. His research interests lie in injury epidemiology, health inequalities, quantitative health impact assessment and the use of linked data to inform policy and decision making.

What is the context for your recent research on novice motorcycle riders?

We know that compared to other road users, motorcycle riders have a disproportionately high risk of crashes that result in serious injury or death. Previous studies have linked measures of rider characteristics (e.g. age, gender, education), riding behaviour (e.g. speeding, riding errors, stunts), reason for riding and riding conditions (e.g. commuting, work, recreation, rain, darkness, heavy traffic), riding experience, type of motorcycle, alcohol use, and road conditions with the risk of motorcycle crashes.

Few studies have investigated multiple crash risk factors and their inter-relationship at the same time, thereby making it possible to identify the factors most strongly associated with the risk of a crash. Also there have been limited studies involving novice riders who have the highest risk of crashing.

What did this research find?

Similar to previous studies - when only considering confounders (age, sex and riding exposure) in the analysis, novice motorcycle riders in this cohort were more likely to have been involved in a crash if they:

• had participated in a pre-learner course;
• held their learner permit and licence for a shorter time;
• did not have prior off-road riding experience;
• rode more kilometres;
• rode more frequently in challenging conditions (heavy traffic, darkness or adverse weather);
• had crashed or reported three or more near-crash events prior to the study or,
• were more prone to errors or engaging in risky riding behaviours.

How does this study contribute new information to existing literature?

After adjusting for rider characteristics, rider training and experience, riding behaviour, riding conditions, purpose of riding, type of motorcycle and riding exposure in the multivariable analysis, only the following measures remained statistically significantly associated with crashing - participation in a pre-learner course, combined time on learner permit and licence, riding exposure before the study, involvement in a near-crash and in a crash before the study.

This indicates that measures of training and riding experience were the strongest predictors of crashing in this group of novice motorcycle riders.

What are the interpretations and implications of this research?

At the time of the study there was no compulsory rider training to obtain a learner permit in the State of Victoria, where it was conducted. It is plausible that riders who voluntarily participated in an unregulated pre-learner course prior to obtaining a learner permit became or remained at high risk of crash after obtaining a rider licence. This may be due to certain characteristics of those who attend such courses (such as being less experienced) or the inability of the range-based programs to sufficiently transfer to on-road environments.

Nonetheless, the findings highlight the need to evaluate the safety benefits of such courses, distinguishing between mandatory versus voluntary courses and whether on-road training is included.

Results also suggest a possible safety benefit of lengthening the time a rider stays on a novice licence (combined learner permit and probationary or restricted licence period).

Since the completion of this this study, Victoria has introduced a graduated licensing system with the aim to improve riding skills and experience and reduce the overrepresentation of novice riders in crash fatalities.

The program comprises three courses: pre-learner (Motorcycle Permit Assessment), learner (Check Ride), and pre-licence (Motorcycle Licence Assessment). Having an interim course between that for the learner permit and the licence is likely to extend the novice licence period and all courses include mandatory on-road training and/or assessment components.

Our findings support the view that such a program might be successful in reducing motorcycle crash rates in novice riders should it provide additional experience for novices. The safety benefits of Victoria’s graduated licensing program and similar initiatives in other jurisdictions should be evaluated to determine if such benefits are realised.

We asked The George Institute’s respiratory expert Professor Christine Jenkins about what the latest data on COVID-19 is telling us, particularly in relation to high risk groups.

What are we learning from China about how the virus is behaving? 

We’re learning a great deal about the clinical illness as papers from Wuhan are published, describing the pattern of COVID illness in large numbers of patients, every week now in the leading medical journals. The most obvious public health learning from China is the value of lockdown, which was implemented later than would have been ideal, but was highly effective in Wuhan. Despite the rapid rise in the number of cases, patients admitted to hospital and deaths, it achieved a rapid reduction in deaths and subsequently a dramatic fall in the number of new cases over a period of only six to eight weeks.  Several papers have since been published which clearly indicate that increasing age is a risk factor for death from COVID-19, although people can die at any age.  Further, it is obvious that coronavirus is quite different to the influenza virus in several key ways.  It is more infectious but it does not appear to infect children at a high rate, which is most unusual for a respiratory virus.  The majority of transmissions are therefore from adult to adult, in a roughly 1:2 ratio (i.e. one infects two others). The lockdown in Wuhan placed a limit on the extent to which other parts of China were affected although it still remains perplexing that the virus did not seriously affect most of the rest of the population in other parts of mainland China. Many questions remain unanswered, in particular how much very mild illness occurred and therefore the size of the “Denominator” – all the people infected with virus. Only when we know this number can we say what the true death rate is from coronavirus infection.

How are people with existing respiratory conditions responding? 

People with existing respiratory conditions usually experience a greater level of symptoms when they have a viral respiratory infection. This is not surprising as they may already be symptomatic from the disease already affecting their lungs, whether it be asthma, COPD or pulmonary fibrosis. On the other hand, a critical question for these people is whether they are more vulnerable to catching the virus or to having a life-threatening consequence from infection.  At this stage it does not appear that they are more vulnerable to catching the virus, but are more vulnerable to serious outcomes from it. There is a very high rate of smoking amongst Chinese men in particular, but at present smoking has not been identified as a risk factor for getting COVID.  As well, the prevalence of smokers amongst people who died from coronavirus in China was no higher than the prevalence of smoking in the general population.

Tell us more about the reported cases of relapse into pneumonia? 

In some people the virus causes a very rapid progression from the onset of symptoms such as fever and cough through to the development of pneumonia, which is usually evidenced by marked breathlessness and low oxygen levels. The pneumonia caused by coronavirus can cause respiratory failure, when the lungs cannot supply adequate oxygen levels to the circulation and vital organs. This can worsen rapidly over a few hours, progressing to a requirement for intensive care admission and assisted ventilation.  In other patients there is a slower evolution of the symptoms and the initial coronavirus symptoms may be mild with a fairly typical illness which lasts three to five days and then appears to improve. Subsequently a few days later some people can deteriorate with pneumonia and respiratory failure.

What does the course of the disease look like in these people and how can they be identified? Is this just in the elderly? 

No, this is definitely not just in the elderly.  Although older people (by which we mean over 60), particularly those with chronic ill-health and comorbidities (such as diabetes, hypertension, lung and heart disease) are more vulnerable to dying from COVID, people can die at any age.  The reasons why somebody who is fit and healthy in their 30s or 40s can die from COVID remains unclear. There may be a constitutional vulnerability to severe effects of viral infection, or alternatively it may relate to the dose of virus they received when they first were exposed.  We have yet to explore the reasons for this in full.

What is your advice to people with existing respiratory conditions? 

People with pre-existing respiratory disease should see their doctors to make sure they are taking the right treatment, receiving their vaccinations, maintaining physical activity and looking after themselves as best as is possible.  This is particularly important in people aged over 60, and in all patients with asthma who tend to be rather relaxed about their preventer treatment if they are feeling well.  It is far better to control asthma well with daily preventer medication than to be vulnerable to a sudden attack when you develop a viral infection.  It is also important that people with asthma use a puffer and spacer to take their reliver medications, rather than nebulisers, as these can spread infection.  They should also ensure they have a written action plan to use in the case of any deterioration. I would encourage all patients with asthma and COPD to discuss their action plan with their GP and make sure they are on the right treatment. Finally but most critically, everyone with lung disease should be taking great care to reduce their risk of coronavirus infection, maintaining hand hygiene and social distancing as advised by health departments.

The George Institute for Global Health, India in its recent rapid evidence synthesis has pointed out that the Frontline Healthcare Workers are at increased risk during COVID-19 even in the course of their normal activities and should be provided with personal protective equipment. The World Health Organisation also has outlined a series of basic protective measures for the frontline health care workers (FLHW) who are at the forefront of fighting the COVID-19 pandemic. This includes protecting oneself and those who come into close contact with others in the community as well. 

However, masks and other personal protective equipment are in short supply in many rural and urban parts of the country and this may put the work of FLHWs at great risk especially when they come into contact with community members. Many frontline health workers confirm this from ground zero. Though this is largely anecdotal, it still underscores the need for the government to be prepared for providing adequate PPE to the FLHWs, a recommendation which the rapid evidence synthesis makes.  

“While working with communities in and around Ballabgarh in Haryana, we noticed that none of the field staff or ASHA worker in the villages had medical masks. It is also not available in local pharmacies,” said Amanpreet Kaur, Research Fellow, The George Institute India, adding the field staff told her that there were few places where they found medical masks, but prices were too high (five times the original price), and the same goes for sanitizers (4-5 times higher price than original).

The situation seems to be no better in villages in and around Palasa in Andhra Pradesh.

“No masks are available in shops and even in the community health centre in Palasa, there seems to be a shortage of masks and aprons,” said Dr Balaji Gummidi, Senior Project Manager, George Institute for Global Health, India who leads a project in Uddanam area of Srikakulam district.

The local administration is aware of the fact that there is scarcity of PPE, he adds.

A similar situation is seen in Vijayawada or in Rohtak.

“It is really heartening to note that the Ministry of Health and family Welfare has come up with guidelines on PPE. We hope that this will ensure that basic personal protective equipment like masks or hand gloves are available in sufficient numbers for the frontline health workers or the health care providers during this hour of crisis,” says Prof Vivekanand Jha, Executive Director, The George Institute India.     

The recently conducted rapid evidence synthesis by a team of researchers from the George Institute India has revealed that FLHWs will be at increased risk of COVID-19 even in the course of normal activities.

“My observation, based on short visits, is consistent with this finding. I can’t but agree with the recommendation that the availability of these life-saving items should be accompanied by training on proper usage in the early phases,” said Amanpreet

These finding acquire an urgent tone, since frontline health care are the backbone of our health activities and cannot practice physical distancing because of the nature of their jobs. It becomes a responsibility of the healthcare system to provide them with appropriate and adequate protection.