Smoking and COVID-19
Manabu Sakuta, Chairman of the Board of Directors
1.

JSTC

17.2.2021

Smoking and the aggravation of COVID-19 symptoms(1) Direct evidence
About 7 days after the onset of initial COVID-19 symptoms, COVID-19 related
pneumonia often becomes more severe. According to novel coronavirus infection(COVID-19) medical treatment guide, version 4.1, of the Ministry of Health, Labor andWelfare; aggravating factors include smoking, being elderly (aged 65 and over), or having
malignant tumors, chronic obstructive pulmonary disease (COPD), chronic kidney disease,
Type 2 diabetes, hypertension or dyslipidemia (high cholesterol). Most of these diseases arealso known to be directly caused by smoking1).

For example, chronic obstructive

pulmonary disease (COPD) is present in 95% of patients who are or were smokers. The
relative risk of contracting end-stage kidney disease from chronic kidney disease is 1.44 forpast smokers and 1.91 for current smokers. The relative risk of type 2 diabetes is 1.44 forcurrent smokers, and smoking is also known to be significantly correlated with dyslipidemia
and obesity.

Smoking also raises the risk of developing cancer in about 20 organs, mainlyin the respiratory system, and it has been reported that active smoking is associated with
90% of lung cancer patients. In sum, smoking is correlated with most kinds of serious
diseases.
Therefore, it therefore seems reasonable that past and present smoking are also associatedwith more severe COVID-19 symptoms.
(2) Epidemiology
Hitherto, several reports have included meta-analysis, but some of these studies aresuspected to have received funding from the tobacco industry.

So when searching theliterature on tobacco, one should reject articles whose authors have conflicts of interest,
articles that have not been peer-reviewed, and articles with studies that violate their inclusion
criteria of test subjects. In these senses, the articles from Miyara et al. and the article fromSimon D et al. should be considered suspect.
In addition, there are five other meta-analysis articles that deserve scrutiny.
Author

JournalPatanavanich
Salah3)
Rahman4)2)Significance of aggravated symptoms or death for smokersNicotine Tob Res

1.9

aggravation

Cureus

2.07

death

Int J Clin Pract

1.71

aggravation

Dai5)
Kunchok6)

China. Front Physiol.

1.825

death

Plos One

1.3

death

Thus, significant values (t-statistics) were found on both sides of two-tailed tests, and it
has already been shown that smoking is significantly correlated with the aggravation ofCOVID-19 symptoms and mortality.
2. Ease of infection(1) Direct evidence
A paper by Tung et al.7) reported that particulate matter (PM2.5 and other diameters)
increases novel coronavirus infections. The paper confirmed in animal experiments and inexperiments with human alveolar cells that the ACE2 receptor acts as an entry point for thenovel coronavirus and that exposure to particulate matter such as PM2.5 increases respiratory
ACE2 receptor expression. It was epidemiologically confirmed that PM 2.5 exposure
increased the mortality rate of the novel coronavirus.
Wu et al.8) examined the relationship between PM2.5 exposure (2000-2016 average level)
and the mortality rate from the novel coronavirus in 3000 counties in the United States, andthe mortality rate was shown to increase 8% for every 1 ㎍/m3 increase in PM2.5 exposure(95% confidence interval 2%-15%) after controlling for 20 variables including population,
age distribution, population density, number of days since an outbreak, number of days
since an announcement of a stay at home order, number of hospital beds, number of PCR
tests, weather, obesity rate and the tobacco smoking rate.

average PM

level
2.5

Mortality rates from the novel
coronavirus

図1
Figure 1

図 2）
Figure 2
In addition, Wu et al. show that PM2.5 exposure increases by about 10 ㎍/m3 to 100 ㎍/m3
from indoor passive smoking (so that a 10 ㎍/m3 increase in exposure increases mortality
rate by 80%).

It is therefore imperative to quit smoking and to eliminate exposure passive

smoking indoors protect against infection from the novel coronavirus.
Environmental Research has recently reported animal experiments from Japan, whichshow how PM2.5 affects the lungs and makes them more susceptible to COVID-19 infection.
According to the report, the amount of protein that the virus sticks to and the amount of

enzymes that the virus uses to enter the cells on the surface of the lungs are dozens of times
higher when exposed to PM2.5.

In brief, the virus can more easily invade lung cells when

they are exposed to PM2.5.
In conclusion, smoking significantly increases PM2.5, and inhaled smoke contains 20,000㎍/m3 of PM2.5. As exposure to PM2.5 increases, it increases ACE2 receptor expression. An
increase of PM2.5 exposure by 1 ㎍/m3 will increase the mortality rate of the novel
coronavirus by 8%. The same relationship applies to passive smoking, and indoor passive
smoking creates PM2.5 exposure of about 10 ㎍/m3 to 100 ㎍/m3.
(2) Epidemiology
A survey of approximately 50,000 representatives of the general population in the United
Kingdom found that smokers are at a 79% higher risk of novel coronavirus infection thannever smokers9). Furthermore, according to Gaiha et al.10), young people who use cigarettes
and e-cigarettes are more susceptible to the novel coronavirus. According to the report, thenumber of people diagnosed with the new coronavirus infection was 5 times higher (95%
confidence interval: 1.82–13.96) for e-cigarette only users (current and past), and 7 times
higher for both tobacco cigarette and e-cigarette users (current and past) (95% confidence
interval: 1.98–24.55) and 6.8 times higher (95% confidence interval: 5.43–15.47) for usersof both in the past 30 days.
According to England's Smoking Toolkit Study11), a monthly survey of England's
population, smokers are now 1.34 times more likely to be infected than never smokers(1.04-1.73).
But the evidence of smoking and infection risk is not robust because even though all
patients are tested for PCR, the tests do not use a random sample from the population, likely
causing a sampling bias.
About 40% of new coronavirus cases are asymptomatic after infection is detected, andabout 2/3 of recent antibody tests in Tokyo show similar results.

Thus, it is necessary to

perform antibody tests on an appropriate sample to determine the population of infected
persons, instead of relying only on results from PCR.
In any case, the incidence of infection remain high, and the effects of PM2.5 data remain
without doubt.
3. In conclusion

I think that it is important that WHO, CDC, and the Ministry of Health, Labor andWelfare explain the danger of smoking during the contagion of the novel coronavirus.
The WHO12) suggests that smoking is associated with increased disease severity andmortality in inpatients infected with COVID-19. Given the established hazards associatedwith tobacco use and exposure to passive smoking, WHO recommends that tobacco users
discontinue use.
CDC13): Current smokers or past smokers are more likely to become seriously ill withCOVID-19.
Ministry of Health, Labor and Welfare14): Risk factors for aggravation: elderly (age 65 andover), malignant tumors, HIV infection (especially CD4 <200/μL)12), chronic obstructive
pulmonary disease (COPD), pregnancy, chronic kidney disease, Type 2 diabetes,
hypertension, dyslipidemia, obesity (BMI 30 and above), smoking, immunodeficiency after
solid organ transplantation.

1) Japan Society for Tobacco Control: Smoking Cessation Studies, 4th Edition, Nanzando,Tokyo, 20192) Patanavanich R, Glantz SA. Smoking is associated with COVID-19 progression. A Metaanalysis. Nicotine Tob Res. 2020; ntaa082.doi:1093/ntr/ntaa082
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239135/
3)Salah HM(Internal Medicine, University of Arkansas for Medical Sciences, Little Rock,Smoking Doubles the Mortality Risk in COVID-19: A Meta- Analysis of Recent Reports andPotential Mechanisms. Cureus. 2020 Oct 7;12(10):e10837. doi: 10.7759/cureus.10837.
PMID: 33173643; PMCID: PMC7647838.
4) Rahman A(Statistics Discipline, Science, Engineering and Technology School, Khulna
University, Khulna, Bangladesh, 9208, Bangladesh.), Bathi NJ. Risk factors of the severity ofCOVID-19: A meta-analysis. Int J Clin Pract. 2020 Dec 7:e13916. doi: 10.1111/ijcp.13916.
Epub ahead of print. PMID: 33372407.
5) Dai M(Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University,Wuhan, China.),et al. Influence of Cigarettes and Alcohol on the Severity and Death ofCOVID-19: A Multicenter Retrospective Study in Wuhan, China. Front Physiol. 2020 Dec
9;11:588553. doi: 10.3389/fphys.2020.588553. PMID: 33362576; PMCID:PMC7756110.

6) Kunchok Dorjee , Hyunju Kim, Elizabeth Bonomo, Rinchen Dolma: Prevalence andpredictors of death and severe disease in patients hospitalized due to COVID-19: A
comprehensive systematic review and meta-analysis of 77 studies and 38,000 patients. PlosOne. Published: December 7, 2020

https://doi.org/10.1371/journal.pone.0243191

7) Tung NT（International PhD Program in Medicine, Taipei Medical University, Taipei,Taiwan; Otorhinolaryngology Department, Cho Ray Hospital, Ho Chi Minh City, Viet Nam）,
Cheng PC, Chi KH, et al. Particulate matter and SARS-CoV-2: A possible model of COVID19 transmission [published online ahead of print, 2020 Aug 5]. Sci Total Environ.
2020;750:141532. doi:10.1016/j.scitotenv.2020.141532
8) Wu X, Nethery RC, Sabath BM, Braun D, Dominici F. Exposure to air pollution andCOVID-19 mortality in the United States: A nationwide cross-sectional study. Preprint.
medRxiv. 2020;2020.04.05.20054502. Published 2020 Apr 7.
doi:10.1101/2020.04.05.20054502
9) Jackson SE(Department of Behavioural Science and Health, University College London,London), Brown J, Shahab L, Steptoe A, Fancourt D. COVID-19, smoking and inequalities:
a study of 53 002 adults in the UK. Tob Control. 2020 Aug 21:tobaccocontrol-2020-055933.
doi: 10.1136/tobaccocontrol-2020-055933. Epub ahead of print. PMID: 32826387; PMCID:
PMC7445100.
10) Gaiha SM(Division of Adolescent Medicine, Department of Pediatrics, Stanford
University, Palo Alto, California), Cheng J, Halpern-Felsher B. Association between youth
smoking, electronic cigarette use and Coronavirus Disease 2019. Journal of Adolescent Health2020; epub ahead of print 11 Aug 2020. https://doi.org/10.1016/j.jadohealth.2020.07.002.
11) Tattan-Birch H, et al. COVID-19, smoking, vaping and quitting: A representative
population survey in England. Addiction. 2020;10.1111
12) WHO : Smoking and COVID-19 Scientific brief 30 June 2020
https://www.who.int/publications/i/item/smoking-and-covid-19
13) CDC: CDC CORONAVIRUS (COVID-19) AND SMOKING UPDATEUpdated Oct. 6, 2020
https://keepitsacred.itcmi.org/2020/10/cdc-coronavirus-covid-19-and-smoking-update/14) Ministry of Health, Labor and Welfare：Medical treatment of COVID-19
https://www.mhlw.go.jp/content/000712473.pdf

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