Active tobacco smoking is associated with lower risk of acquiring SARS-CoV-2 infection among people living with HIV


 SummaryThe relationship between tobacco smoking and SARS-CoV-2 infection is poorly understood. We aimed to assess the impact of current smoking on the risk of COVID-19 acquisition in a well-controlled HIV-infected population. We found that, in this setting, tobacco smoking is associated with a lower risk of acquiring SARS-CoV-2 infection.

have shown an incidence of SARS-CoV-2 infection in this subgroup similar as that found among the general population [2].
The impact of smoking on the risk of developing COVID-19 is unclear and has been a matter of controversy. While some studies have observed an association with an increased severity of COVID-19 [3][4][5], other reports have suggested that the incidence of SARS-CoV-2 infection among current smokers could be lower [6][7][8].
In the present study, we assessed the incidence of SARS-CoV-2 infection in a cohort of HIV-infected patients followed at a hospital in Spain. Our aim was to evaluate the association of current smoking on the probability of developing SARS-CoV-2 infection in PLWH.
We performed a retrospective nested case-control study within a cohort of HIV infected patients followed at the Unit of Infectious Diseases of a University Hospital in Spain. All individuals were evaluated at least every six months until 30 th November 2020 and routinely asked about symptoms consistent with COVID-19. A diagnosis procedure was conducted when any symptom was present. Cases were patients from this cohort with a con rmed diagnosis of COVID-19 between February and October 2020. Control group included the remaining HIV-infected individuals from the cohort without a diagnosis of COVID-19.
Diagnosis of COVID-19 was established by the detection of SARS-CoV-2 RNA or antigen in nasopharynx exudate or bronchial-alveolar lavage, by PCR or EIA, respectively, or by presence of plasma SARS-CoV-2 antibodies by ECLIA. Overall, 394 (56%) individuals of this population were tested for plasma SARS-CoV-2 antibodies as a part of a seroincidence study [9]. Variables that were signi cantly associated with the occurrence of COVID-19 in the bivariate analysis, along with sex and Charlson index, were entered in a logistic regression model, using the enter method. All patients gave informed consent for using their data. This study shows that tobacco smoking is associated with a lower incidence of SARS-CoV-2 infection among PLWH. Despite of higher risk of infection that would be expected among smokers, because of the frequent face touching during smoking act, the probability of being active smoking among participants diagnosed with COVID-19 was 9-fold lower than that of subjects without such a diagnosis.
The role that tobacco may be playing on the risk of SARS-CoV-2 infection is not entirely understood. On one hand, smoking has been reported to be associated with an increased COVID-19 severity [3]. Tobacco smoke exposure results in in ammatory processes in the lung, increased mucosal in ammation, expression of in ammatory cytokines and tumor necrosis factor α, increased permeability in epithelial cells, mucus overproduction, and impaired mucociliary clearance [10], all of which may prompt a more severe lung damage. On the other hand, there are some data suggesting the risk for COVID-19 among smokers could be lower. Thus, in a study conducted in England, a lower incidence of SARS-CoV-2 infection was observed among smokers. Similarly, in a recent meta-analysis (10), whose aim was to assess the impact of tobacco smoking on the risk of developing SARS-CoV-2 infection, current smoking also appeared to be associated with a lower risk of COVID-19.
The underlying mechanisms involved in the protective effect of tobacco are unclear. Nicotine has a marked impact on regulation of the activity of angiotensin-converting enzyme receptors (ACE) [11], which may interfere SARS-CoV-2 entrance into respiratory epithelial cells, thus reducing the risk of infection.
However, Smith et al showed a correlation between higher ACE2 mRNA levels and SARS-CoV-2 infection in a study conducted in human lung tissue from current smokers. In addition, the frequent habit mouthhands of smokers could also boost the risk of infection. Because of all these reasons, a higher risk of infection would be expected [4]. Nevertheless, a recent study performed in mammalian cell culture models has shown that other host molecular factors and pathways can be essential for SARS-CoV-2 infection [12]. Whether the expression of these additional factors is deregulated in current smokers is something that needs to be analyzed, but it might explain the reduced SARS-CoV-2 infection in this population with high levels of ACE2. This study has some limitations. Given its retrospective design, there might be hidden conditions associated with tobacco use that result in less likelihood of SARS-CoV-2 infection. Thus, a greater proportion of individuals who acquired HIV infection through sexual transmission, particularly MSM (65% vs. 45.8%), were no smokers and COVID-19 might be more common in this speci c subset. Nevertheless, the risk factors for HIV-infection were not associated with a higher risk SARS-CoV-2 infection in our study. Similarly, asymptomatic or mild COVID-19 cases may have gone unnoticed among control group.
However, in most COVID-19 cases symptoms are present [13]. Moreover, all subjects included in this study were questioned about COVID-19 symptoms and close contact to patients with con rmed COVID-19.
Those reporting symptoms or close contact to a COVID-19 con rmed case were tested for SARS-CoV-2 infection. In addition, a majority of participants had undergone a SARS-CoV-2 antibody test. In any case, further prospective cohort studies based on serology determinations should clarify this problem.
The molecular and physiological mechanisms by which tobacco smoking might protect against SARS-CoV-2 infection should be further investigated in order to gain insight into potential targets for the prevention and treatment of COVID-19. In the meanwhile, public-facing messages about a possible protective effect of tobacco smoking on the risk of COVID-19 must be avoided, taking into account the high risk for a wide spectrum of extremely severe heath problems associated with tobacco smoking, which counterbalance any protective role of this habit against SARS-CoV-2 infection.