Stopping smoking could improve Covid-19 outcomes

Back to basics: Helping smokers quit could improve Covid-19 outcomes, explains Anthony Clarke

Research into risk factors for Covid-19-related infection, hospitalisation and outcomes is a rapidly evolving field, and no peer-reviewed studies have yet directly evaluated the risk of Covid-19-related hospitalisation among smokers. However, in an effort to gain insight into this risk, the World Health Organization (WHO) recently reviewed data from 34 peer-reviewed studies (26 observational studies and eight meta-analyses) among patients hospitalised with Covid-19.[1] Although these studies did not provide data that would allow for quantification of the risk of SARS-CoV-2 infection or Covid-19-related hospitalisation, the available evidence suggests that there is an association between smoking and the severity of disease/death in patients with Covid-19. Additionally, the Centers for Disease Control and Prevention (CDC) has identified smoking as a factor that may increase the risk of severe illness from Covid-19 for both current and former smokers.[2] Based on these findings and the well-established negative effects of tobacco use on multiple aspects of health, the WHO recommends that tobacco users stop using tobacco, and the CDC recommends that current smokers quit smoking, former smokers refrain from restarting, and that never smokers don’t start.[1, 3]

Covid-19 is just the most recent addition to a long and growing list of conditions for which smoking is a significant risk factor, including cardiovascular disease, stroke, a dozen different types of cancer, chronic obstructive pulmonary disease, type 2 diabetes, rheumatoid arthritis, and reduced male and female fertility.[4] Despite the clearly defined health risks associated with cigarette smoking, nearly 14% of adults in the USA aged 18 years or older smoked cigarettes in 2018, and it is estimated that there are 34 million adults who are current cigarette smokers.[5]

While health professionals often make conversations about smoking status and smoking cessation a routine part of their interactions with patients, the current pandemic offers care providers a new and potentially more urgent reason to engage with patients on the benefits of quitting smoking. Additionally, data recently presented at the Society for Research on Nicotine and Tobacco Virtual Half-Day Conference indicates that the pandemic may be increasing interest in quitting among current smokers, based on analyses of social media activity and Internet searching.[6]

If the pandemic is driving more smokers to consider quitting, how do healthcare professionals help motivated individuals achieve this difficult goal? About 66% of smokers are interested in quitting, and about 50% of smokers receive recommendations to quit from their healthcare providers and have tried to quit in the year following the recommendation. Despite this interest and effort, fewer than 33% of smokers have used evidence-based approaches to quitting, and fewer than 10% successfully quit in a year.[7] While cessation counselling and the use of FDA-approved smoking cessation medication can help increase the likelihood of quitting, the combination of both approaches yields better results.[7]

FDA-approved smoking cessation therapies include nicotine replacement therapy (NRT) and non-nicotine-containing therapies (Chantix [varenicline] and Zyban [bupropion]). The majority of NRTs, which are the most commonly used smoking cessation therapies, are available over-the-counter as skin patches, chewing gum, or lozenges, while one (Nicotrol [Nicotine Inhalation System]) is a prescription medication available as a nasal spray or an oral inhaler. The goal of all NRTs is to provide an alternate source of nicotine that can help reduce nicotine craving and/or withdrawal as individuals cut down on cigarette smoking. Because NRTs are a source of nicotine, they may be contraindicated for people with a variety of health conditions, including diabetes, heart disease, asthma, stomach ulcers, irregular heartbeat and high blood pressure not controlled with medication.[8] Common NRT side effects include headache, nausea and racing heartbeat.

Chantix works in the brain to both mimic the effect of nicotine, which reduces nicotine cravings, and also reduce the rewarding effects of nicotine. The mechanism of action for Zyban has not been determined, but it is known to have multiple central nervous system effects. Although both of these therapies can improve rates of smoking cessation, they are associated with troublesome side effects, the risk of which is the number-one reason that smokers report not using Chantix or Zyban, according to a survey sponsored by Achieve Life Sciences, the company developing cytisinicline, an investigational smoking cessation therapy. Claims data in the USA indicates that 76% of individuals using Chantix fail to complete a three-month course of therapy[9] and the survey referenced above found that 61% of respondents who did not complete their full prescription of Zyban or Chantix indicated that they stopped taking these medications due to side effects.

This data suggests that even individuals who are motivated enough to use a smoking cessation therapy may have difficulty quitting smoking. Healthcare providers may help support these individuals along their smoking cessation journey in several ways. These include recommending participation in smoking cessation counselling or other types of psychological support, proactively identifying and helping to manage cessation-related side effects or withdrawal symptoms, and remaining non-judgmental if patients require more than one attempt to quit successfully.

In addition to the current FDA-approved smoking cessation therapies, clinical trials are ongoing in the USA for cytisinicline as a potential prescription therapy for smoking cessation and nicotine addiction. Cytisinicline is a plant-based, naturally occurring alkaloid that is structurally similar to nicotine and is believed to aid in smoking cessation by binding to the α4β2 nicotinic acetylcholine receptor in the brain. This binding partially stimulates dopamine release, which reduces nicotine cravings and the severity of nicotine withdrawal symptoms. It also directly inhibits nicotine binding, reducing the satisfaction typically associated with smoking.

Cytisinicline is more selective for the α4β2 nicotinic receptor and much less active at 5 HT receptors than Chantix, which may provide a better side effect profile, in particular with respect to nausea/vomiting and sleep disorder/abnormal dreams. A Phase 2b dose optimisation trial evaluating the efficacy, safety, and tolerability of cytisinicline as an aid to smoking cessation was conducted in 254 smokers in the USA. Subjects were treated for 25 days then followed up off treatment for an additional four weeks.[10] The study demonstrated statistically significant quit rates at both the end of treatment and off treatment at weeks five through eight. Smokers who received 3.0 mg cytisinicline dosed TID over 25 days demonstrated a 54% abstinence rate at week four compared to 16% for placebo (p < 0.0001). For weeks five through eight, the four-week continuous abstinence rate was 30% for cytisinicline compared with 8% for placebo (p= 0.005). The Odds Ratios were 6.31 and 5.04 respectively, indicating that cytisinicline was at least five times more effective than placebo at both time points. In this trial, cytisinicline was well tolerated with no serious adverse events reported – in particular, the incidence of nausea was low. A Phase 3 trial is expected to commence in the fourth quarter of 2020.

Until potential new smoking cessation therapies are available, healthcare providers should continue to work with patients who smoke to navigate the difficult journey of smoking cessation successfully. While quitting smoking has always been an important health objective, the current Covid-19 pandemic may provide new opportunities and motivation to begin – and hopefully complete – a journey with known health benefits. Physicians and scientists must continue our efforts to help those who wish to quit smoking achieve this critical goal.

Anthony Clarke, PhD, is president and chief scientific officer, Achieve Life Sciences


1 World Health Organization. Smoking and COVID-19. WHO Scientific Brief. June 30, 2020. Available at

2 Centers for Disease Control and Prevention. Coronavirus Disease 2019 (COVID-19): People with Certain Medical Conditions. Available at: Updated July 7, 2020.

3 Centers for Disease Control and Prevention. Coronavirus Disease 2019 (COVID-19): Smoking. Available at: Updated August 14, 2020.

4 Centers for Disease Control and Prevention. Health Effects of Cigarette Smoking. Available at: Updated April 28, 2020.

5 Centers for Disease Control and Prevention. Current Cigarette Smoking Among Adults in the United States. Available at: Updated November 18, 2019.

6 Cappella JN, et al. Smoking, Quitting and Social Media: Insights from Reddit during the COVID-19 Pandemic. Presented at the Society for Research on Nicotine and Tobacco’s Tobacco, Nicotine & Covid-19 Virtual Conference. July 30, 2020.

7 Babb S, Malarcher A, Schauer G, Asman K, and Jamal A. Quitting Smoking Among Adults – United States, 2000-2015. Centers for Disease Control and Prevention Morbidity and Mortality Weekly Report. 2017;65(52):1457-1464. Available at:

8 U.S. Food and Drug Administration. Want to Quit Smoking? FDA-Approved Products Can Help. Available at:

9 IQVIA Prescription Claims Database; 072018-062019.

10 Nides M, Rigotti N, Benowtiz N, Cain D, Clarke A and Jacobs C. A Multicenter, Double-blind, Randomized, Placebo-controlled Phase 2b Trial of Cytisinicline in Adult Smokers. Presented at the Society for Research on Nicotine and Tobacco Europe 19th Annual Conference in Oslo, September 13, 2019.



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