1 xxxx • DOI: 10.

2478/pneum-2020-0017 • 69 • 2020 • 1-4 1

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3 Pneumologia 3
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7 ‘COVID-19’ a new threat for smokers and vapers? 7
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Florin Mihălţan*, Corina Oprea, Valentin Coşei, Ancuţa Constantin
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12 National Institute of Pneumology “M.Nasta”, Bucharest, Romania 12
13 Abstract 13
14 English: 14
15 The new pandemic disease Covid-19 compelled all the researchers to investigate for early identification of the potential risk 15
16 ­factors. Further, relation between smoking and infections are well known. The authors are trying to find the epidemiological links, 16
the pathogenic mechanisms and also the impact of this coronavirus on different respiratory chronic diseases, based on the last
17 published data about consequences of smoking and vaping on consumers. 17
18 18
Keywords
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vaping • e cigarette • smoking • COVID-19
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Rezumat
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COVID-19 o nouă amenințare pentru fumători și 26
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28 “vapers”? 28
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Rezumat
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33 Romanian: 33
34 O nouă boală pandemică a obligat toți cercetătorii să cerceteze pentru identificarea timpurie a factorilor de risc potenţiali. 34
­Conexiunile fumatului la infecții sunt bine cunoscute. Autorii încearcă să vadă care sunt legăturile epidemiologice, ­mecanismele
35 35
patogenice și, de asemenea, impactul acestui coronavirus asupra diferitelor boli cronice respiratorii, căutând ultimele date
36 ­publicate despre consecințele fumatului și “vapingului” asupra consumatorilor. 36
AQ1 37 Cuvinte-cheie 37
38 xxxx 38
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44 Introduction 44
45 45
46 The year 2020 started with a new pandemic disease is still unclear even though the researchers found a 96% 46
47 COVID-19, spreading rapidly everywhere. More and more DNA match between bat and human coronavirus or they 47
48 alarming signals and information reached the world from suspected pangolins earlier for the disease (1). It is one 48
49 Wuhan, Hubei Province (China) in the last few months. After of the important epidemic diseases of the last century. 49
50 extensive research made by my Chinese colleagues, the Other pandemic diseases in the last 40  years prior to this 50
51 first case (case zero) was reported in November 2019 and challenging disease were: Ebola virus disease in 1976 in 51
52 officially recognised in December (1). A wet market in this the Democratic Republic of Congo and Sudan (fatality rate 52
53 town is found to be and considered as the possible pandemic around 50%), severe acute Respiratory syndrome (SARS) 53
54 origin. The link between humans and the intermediate host (caused by SARS coronavirus) in 2002–2003 (first case in 54
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*Corresponding author: Florin Mihaltan, National Institute of Pneumology “M.Nasta”, Bucharest, Romania.
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E-mail: mihaltan@starnets.ro
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Open Access. © 2020 Mihălțan et al., published by Sciendo
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This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 License.
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 Pneumologia

1 China a mortality rate of 9.6%), Asian Flu (N1H1) in 2009 were former smokers, and on the other sample 0% and 3.7% 1
2 (first case in California, with 0.001–0.007% deaths of the (QR-2,3). In another study (13) the number of smokers 2
3 world population) and Middle East Respiratory Syndrome with severe disease was much higher (12.6%). Further, it is 3
4 (MERS) (caused by a coronavirus (MERS-CoV) in 2012 (first mentioned by Liu et al. in his paper that smoking, as a risk 4
5 case in South Arabia, 35% of reported patients died) (2). factor, is responsible for adverse outcome in patients with 5
6 Now, we have the initial statistics on COVID 19 infection and a history of smoking (27.3%) than the group that showed 6
7 the researchers are working to evaluate the social, health improvement or stabilisation (3.0%) (p=0.018 level) (11). Most 7
8 and economic impact on every nation. On March 13, WHO of these studies were on small samples. The largest study 8
9 said that Europe was the centre of the pandemic (3) but every was conducted by Guan et al. (13). They identified that higher 9
10 European nation approached and tackled this contagious percentages of current and former smokers among patients 10
11 disease and its consequences with different strategies. On needed ICU support, mechanical ventilation or who had 11
12 29 March 2020, the pandemic statistics were: more than died, and a higher percentage of smokers among the severe 12
13 6,84,000 are confirmed with infection, over 32,000 are dead cases. Further, they quantified the risk for smokers vs. non- 13
14 and more than 1,45,000 are recovered (4). We have now smokers; for the first group, it is 1.4 times more likely to have 14
15 started to learn many lessons from the obtained data. severe symptoms of COVID-19 and 2.4 times more likely to 15
16 When risk factors are considered even with the available be admitted to an ICU (on ventilators or to die). 16
17 limited data taking into account risk and prognostic factors, 17
18 smoking is found to be a recognised detrimental factor to the Hypothesis of susceptibility to COVID 19 of smokers 18
19 immune system as well as the responsiveness to a variety It is well known that smokers are vulnerable to virus 19
20 of infections. The outbreak of influenza, MERS, and SARS and countless studies confirming the same. Angiotensin 20
21 brought more severe cases and increased mortality rates converting enzyme 2 (ACE2) has been identified as a receptor 21
22 of smokers or the risk of infections (5,6). But the following for HCoV-19. This generates the hypothesis that smoking 22
23 question ‘what are the links between smoking, vaping, and is responsible for the differences in expression pattern of 23
24 COVID 19’ is still remaining unanswered. We are trying to find ACE2 in the respiratory tract, with consequences related 24
25 the answers starting with the epidemiology of the disease, to the susceptibility to the virus. Three datasets (GSE994, 25
26 possible pathogenic interactions, or therapeutically aspects. GSE17913, and GSE18344) have been evaluated. Elevated 26
27 ACE2 were found in intrapulmonary airways (GSE994) and 27
28 Epidemiology connections oral epithelial cells (GSE17913) of smokers; it was not the 28
29 Vardavas and Nikitara (7) conducted a search about the same for non-smokers or former smokers (14). Data on 29
30 possibility of the association between smoking-severity of human as well as experimental research on rats confirmed 30
31 COVID 19 infections, the need for ventilation, need of ICU, that smoking is increasing ACE2 in the respiratory tract and 31
32 and rate of hospitalisation or death. They screened 71 also the susceptibility to HCoV-19.  Smoking can upregulate 32
33 studies and finally, only 5 from China were selected by the this angiotensin-converting enzyme-2 (ACE2) receptor which 33
34 authors. Their idea was following the first 2  months of the is recognised as receptor for other coronavirus infections 34
35 COVID 19 pandemic (December 2019 and January 2020) such  as SARS, SARS-CoV, and the human respiratory 35
36 and registering the data, and found that the mortality rate of coronavirus NL638 (15). ACE2 could be a novel adhesion 36
37 smokers is 9% (8). General mortality in China due to COVID molecule for SARS-CoV-2 causing COVID-19. So, it can be a 37
38 19, was 3.6% (9). Consistent with these 5 studies, analysis of potential therapeutic target for the prevention of fatal microbial 38
39 deaths due to coronavirus in China shows that men are more infections and the same type of upregulation is possible 39
40 likely to die than women, which may be probably related to for e-cigarette and heat-not-burn IQOS devices (15). Using 40
41 the fact that many Chinese men smoke more than women RNAseq, Leung et al. (16) determined gene expression levels 41
42 (10). WHO report on the global tobacco epidemic, China in bronchial epithelia obtained from cytological brushings of 42
43 Country Profile 2019, demonstrated that 52.1% of Chinese 6th to 8th generation airways in individuals with and without 43
44 men smoke compared to just 2.7% of women. Another strong COPD. They found an increasing ACE2 expression in 44
45 argument coming from these studies is about the factors lower airways in patients with COPD and current smokers. 45
46 and chances against and of disease progression (including Moreover, they suggest that these patients are at increased 46
47 death). Moreover, Chinese authors reported that there is a risk of serious COVID19 infection and highlight the importance 47
48 14 times higher risk of having pneumonia among people with of stopping smoking in reducing the risk. 48
49 a history of smoking compared to those who did not smoke The other well-known effect of smoking is vasospasm 49
50 (11). Zhang and et al. (12), after analysing the mortality and and transient hypoxia of organs induced by a high level of 50
51 the severity of diseases, found that among the severe vs. blood nicotine. The depletion of oxygen in the viscera and 51
52 nonsevere patients, 3.4% were current smokers and 6.9% the respiratory tract will reduce immunity significantly (17). 52

2

Dissemination of COVID 19 infection depends also on the
one’s smoking habits; that’s why in between the personal
precocious recommendations coming from the specialist it’s
also included quitting smoking
E cigarette and COVID-19
Just like the discussion on vaping divided the medical schools
between the defenders and opponents for 2 years, the
discussion on the consequences of COVID 19 on the dangers
of vaping and e cigarette have split the community into two.
For some authors (18) there are no evidence that vaping
(intrinsically) increases the risk of infection or progression
to severe condition of COVID-19; they consider it as effect
of COVID19 linked to previous conventional smoking. They
sustained also that even propylene glycol is working as a
disinfectant. That’s why these authors have only some plain
recommendations like (18,19):
• If you vape, do not revert to smoking (if you are a dual user
try to become an exclusive vaper).
• If you enjoy vaping and do not smoke, quitting vaping must
be a personal choice and not an obligation.
• Be discreet and do not call unwanted attention (bear in
mind that these are difficult times and that a lot of non-
vapers have been exposed to a lot of misinformation).
• Avoid big clouds in public at all costs (even outdoors).
• Use low powered devices whenever possible and when
others are around. The risk of spreading the virus with
discrete vaping in low powered devices is roughly equivalent
to the risk of spreading it through normal sedentary breathing.
• Avoid vaping in enclosed public spaces and try to keep at
least 2 m distance from others when vaping outdoor.
Contrarily Prof Glantz (20), recognised as an objective
researcher (without any sponsoring activities from the
tobacco industry), stated that vaping like smoking may also
harm lung health; his arguments are based on the well-
known demonstrated effects of e-cigarette on the lung (21,22)
(impaired mucociliary clearance and neutrophil phagocytosis,
damage of the lung by the effect of neutrophils lyse DNA
and release it into the extracellular environment to help to
immobilize bacteria and enhance of upper airway colonization
and tissue damage by aerosol exposure). Because of these,
including stopping smoking, vaping, and avoiding second-
hand exposure are the lists of important preventive measures
according to his opinion. Even the FDA stated in an email that
e-cigarette use can damage lung cells (23).
Smoking and different diseases. What we already know
In lung cells including bronchial epithelial cells, alveolar
macrophages, pulmonary endothelial cells, and interstitial
fibroblasts, nicotinic receptors are co-expressed with most
Mihălțan et al.: ‘COVID-19’ a new threat for smokers and vapers
components of the RAS (renin–angiotensin system) (24).
Smoking is already known for increasing the risk for the
development of acute respiratory distress syndrome (ARDS)
on people associated with different risk factors like: severe
infection, non-pulmonary sepsis (blood infection), or blunt
trauma (25, 20). Regarding the cancer patients with smoking,
the higher rate of smoking history can be one of the potential
factors of higher risk of COVID-19, and with a poorer prognosis
than those without cancer (26). The same authors describe
these cancer patients in the sample are prone to severe
conditions and events (admission to the intensive care unit
requiring invasive ventilation, or death) due to COVID-19. For
COPD patients after adjusting for age and smoking status,
COPD hazards ratio (HR) was 2.681(95% confidence interval
1.424–5.048) (27). The number of comorbidities is also an
important factor. Smoking is a trigger for asthma and at the
same time smoking can weaken lung function. When you
have asthma, if you smoke, your lung capacity will deteriorate
very rapidly. Smoking when children with asthma are near to
you will affect their lung function too (28).
Conclusions
Many relations are established at this moment by demonstrating
the smoker’s vulnerability to COVID-19. If more cases are
being examined in the coming months (from different ethnic
and genetic backgrounds worldwide), probably this ACE2
expression variation can be better analysed and compared to
establish whether and when it contributes to susceptibility to
COVID-19 and it will be more simple to find some subgroups
or phenotypes.(29) But, it is certain for smokers with COVID
19 infections, there will be a greater impact on disease
progression; association with smoking is most likely with the
negative progression and adverse outcomes of COVID-19.
Further, WHO and all countries should ensure for the next
pandemic waves that the smoking status of patients identified
with Covid-19, including deaths, is recorded and incorporated
in data sets for determining this important relationship of
the virus with an external risk factor. Data on vaping and
COVID-19 are now collected and we are confident that the
next articles will be able to analyse on deleterious effects of
e-cigarette effectively and more convincingly.
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