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A nicotinic hypothesis for Covid-19 with preventive and therapeutic implications


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SARS-CoV-2 epidemics raises a considerable issue of public health at the planetary scale. There is a pressing urgency to find treatments based upon currently available scientific knowledge. Therefore, we tentatively propose a hypothesis which hopefully might ultimately help save lives. Based on the current scientific literature and on new epidemiological data which reveal that current smoking status appears to be a protective factor against the infection by SARS-CoV-2 [1], we hypothesize that the nicotinic acetylcholine receptor (nAChR) plays a key role in the pathophysiology of Covid-19 infection and might represent a target for the prevention and control of Covid-19 infection.
Comptes Rendus
Jean-Pierre Changeux, Zahir Amoura, Felix A. Rey and Makoto
A nicotinic hypothesis for Covid-19 with preventive and therapeutic
Volume 343, issue 1 (2020), to appear.
© Académie des sciences, Paris and the authors, 2020.
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2020, 343, n1, to appear
News and events/ Actualités
A nicotinic hypothesis for Covid-19 with preventive
and therapeutic implications
Une hypothèse nicotinique pour Covid 19 et ses implications
préventives et thérapeutiques
Jean-Pierre Changeux ,a, Zahir Amoura b,c, Felix A. Reydand Makoto Miyarab,e
aInstitut Pasteur CNRS UMR 3571 Department of Neuroscience and Collège de
France, Paris France
bSorbonne Université, Inserm UMRS, Centre d’Immunologie et des Maladies
Infectieuses (CIMI-Paris)
cAssistance Publique-Hôpitaux de Paris, Groupement Hospitalier Pitié-Salpêtrière,
Service de Médecine Interne 2, Maladies auto-immune et systémiques Institut E3M
dInstitut Pasteur, Structural Virology Unit, Department of Virology, CNRS UMR 3569,
Institut Pasteur Paris France
eAssistance Publique-Hôpitaux de Paris, Groupement Hospitalier Pitié-Salpêtrière,
Département d’Immunologie, Paris, France.
Abstract. SARS-CoV-2 epidemics raises a considerable issue of public health at the planetary scale.
There is a pressing urgency to find treatments based upon currently available scientific knowledge.
Therefore, we tentatively propose a hypothesis which hopefully might ultimately help savelives. Based
on the current scientific literature and on new epidemiological data which reveal that currentsmoking
status appears to be a protective factor against the infection by SARS-CoV-2 [1], we hypothesize that
the nicotinic acetylcholine receptor (nAChR) plays a key role in the pathophysiology of Covid-19
infection and might represent a target for the prevention and control of Covid-19 infection.
Résumé. L’épidémie de SARS-Cov-2 pose un problème considérable de santé publique à l’échelle
planétaire. Il y a urgence extrême de découvrir des traitements qui se fondent sur les connaissances
scientifiques disponibles. Nous proposons donc une hypothèse plausible mais provisoire qui puisse le
moment venu contribuer à sauver des vies. Elle se fonde sur la littérature scientifique disponible et sur
des données épidémiologiques nouvelles qui révèlent que le statut de fumeur parait être un facteur
de protection contre l’infection par SARS-Cov-2 [1]. Nous proposons l’hypothèse que le récepteur
nicotinique de l’acétylcholine (nAChR) joue un rôle critique dans la pathophysiologie de l’infection
Covid-19 et puisse représenter une cible pour la prévention et le contrôle de l’infection.
Keywords. Covid-19, smoking, nicotinic receptors, clinical trials of nicotine patches.
Mots-clés. Covid-19, fumeurs, récepteurs nicotinique, essais clinique patch nicotine.
Manuscript received 16th April 2020, accepted 18th April 2020.
Corresponding author. Jean-Pierre Changeux and Zahir Amoura are equal first authors.
ISSN (electronic) : 1768-3238 https://comptes-rendus.academie-
2Jean-Pierre Changeux et al.
Symptomatic Covid-19 disease (as caused by
SARS-CoV-2 virus) is observed in 2.5 percent of in-
fected individuals [2] indicating an individual vari-
ability in the clinical presentation. Among the epi-
demiological and clinical features of Covid-19, the
following features are of special interest for un-
derstanding the patho-physiolology, namely: (1) in
outpatients with favorable outcome : neurologi-
cal/psychiatric disorders, especially loss of sense of
smell which is specific of the disease and (2) in hos-
pitalized older patients with a poor prognosis : sys-
temic hyperinflammatory syndrome with increased
levels of circulating cytokines and atypical acute res-
piratory distress syndrome with loss of neurological
control of lung perfusion regulation and hypoxic
vasoconstriction [3]. This raises the issue of the basis
of inter-individual variability for the susceptibility to
The nAChR appears as a hypothetical clue for
the main clinical manifestations of Covid-19. It is
accepted that the angiotensin converting enzyme 2
(ACE2), represents the principal receptor molecule
for SARS-CoV-2 [4–6]. ACE2 is expressed at the tran-
scriptomic level in the lung, the small intestine and
colon, in the kidney, in the testis, in the heart mus-
cle and in the brain, yet the protein is not detected
in the lung [7]. In the brain, ACE2 is expressed in
both neurons and glia and particularly present in
the brain stem and in the regions responsible for
the regulation of cardiovascular functions, including
the subfornical organ, paraventricular nucleus, nu-
cleus of the tractus solitarius, and rostral ventrolat-
eral medulla [8]. Additional receptors or co-receptors
are, however, not excluded. The relationship between
nicotine and ACE2 has been explored in the frame-
work of cardiovascular and pulmonary diseases [9].
Accordingly, in the ACE/ANG II/AT1R arm, nicotine
increases the expression and/or activity of renin, ACE
and AT1R, whereas in the compensatory ACE2/ANG-
(1–7)/MasR arm, nicotine down regulates the expres-
sion and/or activity of ACE2 and AT2R, thus suggest-
ing a possible contribution of acetylcholine receptors
in ACE2 regulation. This possibility has not yet been
explored in the framework of viral neuroinfections.
There is strong evidence for a neurotropic action
of SARS-CoV-2 infection. It has been demonstrated
that β-coronaviruses to which the SARS-CoV-2 be-
longs, do not limit their presence to the respiratory
tract and have been shown to frequently invade the
CNS [10]. This propensity has been convincingly doc-
umented for the SARS-CoV-1, MERS-CoV and the
coronavirus responsible for porcine hemagglutinat-
ing encephalomyelitis (HEV 67N). In light of the high
similarity between SARS-CoV-1 and SARS-CoV-2, it is
quite likely that SARS-CoV-2 also possesses a similar
potential. Neuroinfection has been proposed to po-
tentially contribute to the pathophysiology and clin-
ical manifestations of Covid-19 [10] with the neu-
roinvasive potential of SARS-CoV-2 suggested to play
a role in the respiratory failure of Covid-19 patients
[11, 12]. Our nicotinic hypothesis proposes that the
virus could enter the body through neurons of the
olfactory system and/or through the lung leading to
dierent clinical features with dierent outcome, and
contrasts with the currently accepted view that ACE2
is the principal receptor of SARS-CoV-2 for its entry
into cells.
As mentioned, loss of sense of smell frequently
occurs in Covid-19 patients [13]. Furthermore, sev-
eral studies have reported that some patients in-
fected with SARS-CoV-2 show neurologic signs such
as headache (about 8 %), nausea and vomiting (1 %)
[11]. More recently, a study of 214 Covid-19 patients
[14] further found that about 88 % (78/88) of the se-
vere patients displayed neurologic manifestations in-
cluding acute cerebrovascular diseases and impaired
consciousness. Based on an epidemiological survey
on Covid-19, the median time from the first symp-
tom to dyspnea was 5.0 days, to hospital admission
was 7.0 days, and to the intensive care was 8.0 days
[15]. Therefore, the latency period may be adequate
for the virus to enter the nervous system, invade the
brain stem and aect the medullary neurons of the
respiratory centers. However, variability of the neuro-
logical signs was observed with patients having anos-
mia, showing in general a mild evolution without pul-
monary attack, in contrast with those without anos-
mia suggesting a diversity in the mode of prolifera-
tion and /or progression of the virus.
More than 20 years ago, Mohammed, Norrby &
Kristensson [16], in a pioneering study, showed with
a broad diversity of viruses (Poliovirus, Herpes sim-
plex virus, West Nile virus , Vesicular Stomatitis Virus,
influenza H1N1 virus [17]), that viruses enter the ol-
factory epithelium and progress first through the ol-
factory pathway in an anterograde direction and then
in a retrograde manner to the reticular neurons pro-
jecting to the olfactory bulbs, the median raphe neu-
C. R. Biologies,2020, 343, n1, to appear
Jean-Pierre Changeux et al. 3
rons (serotoninergic) and the ventral and horizontal
diagonal band (cholinergic) [16,18]. This olfactory in-
fection route scheme [18] has been recently extended
to Covid-19 infection [2, 11]. To further investigate
the molecular aspects of Covid-19 propagation in
the brain and its pharmacology, we have been aided
by abundant studies on rabies virus (RABV) a nega-
tive polarity, single-strand RNA virus that is distinct
from the coronaviruses [18–20]. nAChRs were shown
to be the first receptors for RABV [21]. Structural
studies further revealed that a short region in the
ectodomain of the rabies virus glycoprotein shows
sequence similarity to some snake toxins [20, 22]
that were initially used to isolate the nAChR from
fish electric organs [23]. These snake toxins [24] are
known to bind with high anity and exquisite selec-
tivity to the peripheral muscle receptor, while also to
some brain receptors [25,26]. The neurotoxin-like re-
gion of the rabies virus glycoprotein inhibited acetyl-
choline responses of α4β2 nAChRs in vitro, as did
the full length ectodomain of the rabies virus gly-
coprotein [20]. The same peptides significantly al-
tered a nAChR elicited behaviour in C. elegans and in-
creased locomotor activity levels when injected into
the CNS of mice [20]. The nAChR thus plays a criti-
cal role in the host-pathogen interaction in the case
of the RABV. Furthermore, a broad variety of nAChR
oligomers are distributed throughout the brain, in-
cluding the reticular core neurons and the spinal
cord, with the α4β2 and α7 nAChR oligomers being
the most frequent [27]. The hypothesis we wish to ex-
plore is to what implications these data may hold for
SARS-CoV-2 infection and we suggest a strong role of
nAChR in the disorder.
The nAChR pathway is hypothesized to be en-
gaged in the Covid-19 inflammatory syndrome.
The nervous system, through the vagus nerve,
can significantly and rapidly inhibit the release of
macrophage TNF, and attenuate systemic inflam-
matory responses [28]. This physiological mech-
anism, termed the ‘cholinergic anti-inflammatory
pathway’ has major implications in immunology
and in therapeutics. The cytokine production of
macrophages—one of the main cell types found
in the bronchoalveolar fluid—is under the phys-
iological control of auto/paracrine acetylcholine
through their nAChRs [29]. Following dysregulation
of macrophage nAChRs, the profile of cytokines
massively secreted include Il1, Il6, TNF et Il18. This
cytokine profile shows striking analogies with the
cytokine storm syndrome, leading to the hyper-
inflammatory syndrome described in a subgroup
of Covid-19 patients [30]. Systemic coagulopathy
with venous and arterial thrombosis is one of the
critical aspects of the morbidity and mortality of
Covid-19. In line with our hypothesis, one should
note that hematopoietic α7-nAChR deciency in-
creases platelet reactive status, which could explain
the thrombogenic presentation of Covid-19 [31]. Al-
though selective cytokine blockers (eg, IL1-receptor
antagonist anakinra or anti-IL6 tocilizumab) have
been proposed for the control of Covid-19 cytokine
storm, their ecacy is still to be explored. Interest-
ingly, α7 agonists, including nicotine, have proven
to be eective in reducing macrophage cytokine
production and inflammation in animal models of
pancreatitis [32] and peritonitis [33]. In this setting,
a nicotinic treatment that might possibly antago-
nize the blocking action of SARS-CoV-2 on the AChR
through a possible modulation of the ACE2 – nAChR
interaction, would act earlier than anti-cytokine
therapies. nAChR modulation by Covid-19 might
tentatively account for the hyperinflammatory fea-
tures observed in a subgroup of Covid-19 patients,
mimicking bona fide the macrophage activation
Of note, our hypothesis could explain the high
prevalence of obesity and diabetes mellitus observed
in severe forms of Covid19. The diminished vagus
nerve activity previously described in these two ill-
nesses could be potentiated by the Covid-19 elicited
nicotinic receptor dysregulation, leading to a hyper-
inflammatory state often reported in obese patients
nAChRs are present in the lung epithelium. The
non-neuronal cholinergic system contributes to the
regulation of cell functions such as cell-cell interac-
tion, apoptosis, and proliferation and it is well estab-
lished that human bronchial epithelial cells contain
nAChRs. The airway epithelium expresses α3, α4, α5,
α7, α9, β2, and β4-nAChRs subunits [34–37] and
their contribution has been discussed in the frame-
work of airway epithelial basal cell proliferation-
dierentiation and their alteration in lung cancers
[38]. These nAChRs are mentioned here as possi-
ble targets of Covid-19 infection of the lung, which
would take place concomitantly with, and/or as a
consequence of, the neuro-infection. Additionally,
C. R. Biologies,2020, 343, n1, to appear
4Jean-Pierre Changeux et al.
nAChRs are involved in lung perfusion regulation,
which seems to be disrupted in the atypical acute res-
piratory distress syndrome reported in Covid-19 pa-
tients [3].
A potential protective eect of smoking and of
nicotine on SARS-CoV-2 infection has been noted.
Until recently [39], no firm conclusions could be
drawn from studies evaluating the rates of current
smokers in Covid-19. All these studies [40–48], al-
though reporting low rates of current smokers, rang-
ing from 1.4 % to 12.5 %, did not take into account
the main potential confounders of smoking includ-
ing age and sex. In the study that two of us are re-
porting [1], the rates of current smoking remain be-
low 5 % even when main confounders for tobacco
consumption, i.e. age and sex, in- or outpatient sta-
tus, were considered. Compared to the French gen-
eral population, the Covid-19 population exhibited
a significantly weaker current daily smoker rate by
80.3 % for outpatients and by 75.4 % for inpatients.
Thus, current smoking status appears to be a protec-
tive factor against the infection by SARS-CoV-2. Al-
though the chemistry of tobacco smoke is complex,
these data are consistent with the hypothesis that its
protective role takes place through direct action on
various types of nAChRs expressed in neurons, im-
mune cells (including macrophages), cardiac tissue,
lungs, and blood vessels.
Mechanisms engaged in Covid-19 as nAChR
disease might be tentatively suggested. There is
structural evidence supporting the hypothesis that
SARS-CoV-2 virus is a nicotinic agent. The recently
reported X-ray structure of the RABV glycoprotein (G)
ectodomain [49] shows that the region correspond-
ing to the neurotoxin-like peptide is exposed at the G
surface, in agreement with the fact that this region is
part of the major antigenic region II of RABV [50]. The
recently published cryo-EM structure of the trimeric
SARS-CoV-2 spike (S) protein [51, 52] revealed an
insertion with respect to that of SARS-CoV-1, in a
loop that is disordered in the reported structure, and
which has a polybasic sequence that corresponds
to a furin site. Importantly, this exposed loop of the
SARS-CoV-2 S protein also contains a motif that is
homologous to that of snake neurotoxins and to
the RABV neurotoxin-like region (Figure 1). This ob-
servation supports the hypothesis that SARS-CoV-2
virus itself is a nAChR blocker.
Figure 1. The neurotoxin motifs. Amino acid
sequence alignment of the motifs found in tox-
ins from snakes of the Ophiophagus (cobra)
and Bungarus genera, in G from three RABV
strains and in S from SARS-CoV-2.
Nicotine may be suggested as a potential preven-
tive agent against Covid-19 infection. Both the epi-
demiological/clinical evidence and the in silico find-
ings may suggest that Covid-19 infection is a nAChR
disease that could be prevented and may be con-
trolled by nicotine. Nicotine would then sterically
or allosterically compete with the SARS-CoV-2 bind-
ing to the nAChR. This legitimates the use of nico-
tine as a protective agent against SARS-CoV-2 infec-
tion and the subsequent deficits it causes in the CNS.
Thus, in order to prevent the infection and the retro-
propagation of the virus through the CNS, we plan
a therapeutic assay against Covid-19 with nicotine
(and other nicotinic agents) patches or other delivery
methods (like sning/chewing) in hospitalized pa-
tients and in the general population.
In conclusion, we propose, and try to justify, the
hypothesis that nAChRs play a critical role in the
pathophysiology of SARS-CoV-2 infection and as a
consequence propose nicotine and nicotinic orthos-
teric and/or allosteric agents as a possible therapy
for SARS-CoV-2 infection. Interestingly, ivermectin,
which has been recently shown to inhibit the replica-
tion of SARS-CoV-2 in cells in vitro [53], is a positive
allosteric modulator of α7 nAChR [54]. The nicotinic
hypothesis might be further challenged by additional
clinical studies and by experimental observations de-
termining whether SARS-CoV-2 physically interacts
with the nAChR in vitro, for instance by electrophys-
iological recordings, high resolution EM and by ani-
mal model studies. Further work should also specify
the still enigmatic relationships between ACE2 and
nAChRs in the nervous system.
One should not forget that nicotine is a drug of
abuse [55] responsible for smoking addiction. Smok-
C. R. Biologies,2020, 343, n1, to appear
Jean-Pierre Changeux et al. 5
ing has severe pathological consequences and re-
mains a serious danger for health. Yet under con-
trolled settings, nicotinic agents could provide an
ecient treatment for an acute infection such as
We would like to specially thank Pr. Serge Haroche
for establishing the contact between JPC and ZA.
We thank Dr. Pablo Guardado Calvo (Institut Pas-
teur, Paris) for the amino acid sequence analysis of
the neurotoxin motif, Pr. Florence Tubach for fruit-
ful discussions, Pr. Gérard Orth for valuable support
and discussions, Pr. Daniel Louvard and Pr. Henri
Korn for encouragements. JPC acknowledges useful
exchanges with Dr. Abdul Mohammed and Dr. Kister
Kristensson at early stages of the reflection and the
Pasteur Institute shared discussions network orga-
nized by the Neuroscience Department and its for-
mer Chairman Pr. PM Lledo. We thank Dr. Kurt Sailor
for carefully editing the text.
Competing financial interests
The authors declare no competing financial interests.
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... Some literature suggests that nicotine in tobacco plays an important role in alleviating symptoms of COVID-19 (Changeux et al., 2020). Changeux et al. (2020) found that nicotine-type acetylcholine leads to frequent loss of smell and neurological symptoms (headache, nausea, vomiting) in COVID-19 patients. ...
... Some literature suggests that nicotine in tobacco plays an important role in alleviating symptoms of COVID-19 (Changeux et al., 2020). Changeux et al. (2020) found that nicotine-type acetylcholine leads to frequent loss of smell and neurological symptoms (headache, nausea, vomiting) in COVID-19 patients. ...
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COVID-19 has been of great concern since it broke out. Many countries have put more effort into securing vaccines and therapeutic medicines. In the meantime, there has been a large number of scholarly efforts in figuring out the relationship between smoking and new coronary pneumonia. This study firstly collected daily data (the number of people hospitalized with new coronary pneumonia, severe cases, and the number of people double-vaccinated against new coronary pneumonia in various countries or regions) and annual data (the human development index and smoking rate of each country or region). We collected data from 160 countries from the Our Data World database. The time is for January 1, 2020 through June 30, 2022. We divided daily and annual data into the first-level and second-level data. Finally, we checked the relationship between smoking and COVID-19 in a Hierarchical Linear Model (HLM). The result shows that smoking raises the number of new cases of infection and death among people fully vaccinated per hundred. There is a partial mediating effect of new cases smoothed per million over new deaths smoothed per million. Smoking significantly increases the effect of new cases smoothed per million over new deaths smoothed per million. Our findings have high generalizability around the world.
... The reduced risk of SARS-CoV-2 infection among smokers has been hypothesized to be linked to the effect of nicotine on the nicotinic acetylcholine receptor (nAChR). This effect would result in a reduction in potential sites for viral entry into the pulmonary alveolar epithelium and the inhibition of pro-inflammatory cytokines [36,37]. However, the role of cigarette smoking in the SARS-CoV-2 infection is still debated. ...
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Factors associated with SARS-CoV-2 infection risk are still debated. This case–control study aims to investigate the possible relationship between SARS-CoV-2 infection, evaluated through antibody response, and the main sociodemographic, occupational, clinical-anamnestic, and biochemical factors in a population of Modena province (Northern Italy), mainly workers. Both workers who voluntarily joined the screening campaign proposed by companies and self-referred individuals who underwent serological testing were enrolled. Subjects with antibody positivity were recruited as cases (n = 166) and subjects tested negative (n = 239) as controls. A questionnaire on sociodemographic, occupational, and clinical data was administered through telephone interviews. Serum zinc/iron/copper/chromium/nickel, vitamins D/B12, folates, triglycerides, and LDL/HDL/total cholesterol were measured. Cases lived more often in urban areas (61.8% vs. 57%). Cases and controls did not differ significantly by working macrocategories, but the percentage of workers in the ceramic sector was higher among cases. Low adherence to preventive measures in the workplace was more frequent among seropositives. Folate concentration was significantly lower among cases. Therefore, adequate folate levels, living in rural areas, and good adherence to preventive strategies seem protective against infection. Workers in the ceramic sector seem to be at greater risk; specific factors involved are not defined, but preventive interventions are needed.
... To elucidate the inverse relationship between smoking and COVID-19 risk, several hypotheses have been posited: one suggests that smoking could activate the aryl-hydrocarbon receptor (AHR), possibly suppressing the angiotensin-converting enzyme 2 (ACE2) receptor which the virus uses for cellular entry [9]; another underscores the potential of nicotine to modulate inflammation [10,11]; and yet another speculates on nitric oxide's toxic influence on the virus [12]. All these hypotheses remain speculative. ...
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Background: The association between tobacco use and COVID-19 is controversial. During the early course of the pandemic, limited testing prevented studying a wide spectrum of clinical manifestations. Objective: To examine the potential causal association between tobacco use and COVID-19 during the second wave (1 October 2020–30 June 2021) of the pandemic in Stockholm, Sweden. Methods: A population-based cohort study was conducted in the Stockholm region of Sweden, with information on tobacco use collected prior to the pandemic. Adjusted relative risks (RR) of COVID-19 and 95% confidence intervals (CI) were calculated, contrasting current smokers and snus users to non-users of tobacco. Results: Compared with non-users of tobacco, current smokers had a lower risk of COVID-19 (RR 0.78, 95% CI = 0.75–0.81) and of hospitalisation for the disease. Current s nus users had a higher risk of COVID-19. Heavy smokers and snus users had longer hospital stays than non-users of tobacco. Conclusion: Tobacco use may have a different impact on the risk of being infected with SARS-CoV-2 and the risk of developing severe clinical manifestations. Further research is needed to determine the underlying mechanisms.
... 12 α7 nicotinic acetylcholine receptor (α7-nAChR) activation which is mainly expressed by B cells, T cells, and macrophages, decreases proinflammatory cytokines formation as interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) by nicotine or nicotinic agonists. 13,14 Also, increased inflammatory cytokine may follow disruption of the polarization mechanism of M1 type macrophage through the antagonistic action on α7-nAChRs by SARS-CoV-2. 15 This explains the cytokine storm and the hyperinflammatory syndrome seen in several COVID-19 patients. ...
... 5 Remarkably, prior studies on the impact of smoking on the clinical severity of coronavirus disease 2019 (COVID- 19) have shown conflicting results. In the early COVID-19 pandemic, some claimed protective effects of nicotine (mainly biological aspects on cell receptors) against COVID-19 infection [6][7][8] ; however, recent evidence suggests that nicotine (from any tobacco products) does not protect against COVID-19. 4,9,10 The current evidence suggests that conventional cigarette smoking is associated with a greater risk of severe COVID-19 symptoms, as evidenced by the need for hospitalization. ...
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Background Smoking and vaping are linked to lung inflammation and lowered immune response. Objective Examine the prevalence of coronavirus disease 2019 (COVID‐19) cases, testing, symptoms, and vaccine uptake, and associations with tobacco product use. Methods Data came from the 2021 National Health Interview Survey. The 2021 Sample Adult component included 29,482 participants with a response rate of 50.9%. We investigated COVID‐19‐related outcomes by tobacco product use status and reported national estimates. Multivariable regression models were performed accounting for demographics (e.g., age, sex, poverty level), serious psychological distress, disability, and chronic health conditions. Results In our regression analyses, odds of self‐reported COVID‐19 infection were significantly lower for combustible tobacco product users (vs. nonusers; adjusted odds ratio [AOR = 0.73; 95% confidence interval [CI] = 0.62–0.85]). Combustible tobacco users also were less likely to report ever testing for COVID‐19 (AOR = 0.88; 95% CI = 0.79–0.98), ever testing positive for COVID‐19 (AOR = 0.66; 95% CI = 0.56–0.77), and ever receiving COVID‐19 vaccine (AOR = 0.58; 95% CI = 0.51–0.66) compared with their nonuser peers. Compared to nonusers, users of any type of tobacco who contracted COVID‐19 had higher odds of losing smell (AOR = 1.36; 95%CI = 1.04–1.77), which was more pronounced among exclusive e‐cigarette users. The odds of receiving vaccine were lower for all current exclusive tobacco product users compared to nonusers (AORs = 0.40 to 0.70). Conclusions Continued monitoring of tobacco product use and its association with respiratory diseases such as COVID‐19 is crucial to inform public health policies and programs. In addition, efforts to promote vaccination, especially among tobacco product users, are warranted.
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Background : Coronavirus disease 2019 (COVID‐19) is a pandemic disease caused by severe acute respiratory syndrome CoV type 2 (SARS‐CoV‐2). COVID‐19 is higher in men than women and sex hormones have immune‐modulator effects during different viral infections, including SARS‐CoV‐2 infection. One of the essential sex hormones is progesterone (P4). Aims : This review aimed to reveal the association between P4 and Covid‐19. Results and Discussion : The possible role of P4 in COVID‐19 could be beneficial through the modulation of inflammatory signaling pathways, induction of the release of anti‐inflammatory cytokines, and inhibition release of pro‐inflammatory cytokines. P4 stimulates skew of naïve T cells from inflammatory Th1 toward anti‐inflammatory Th2 with activation release of anti‐inflammatory cytokines, and activation of regulatory T cells (Treg) with decreased interferon‐gamma production that increased during SARS‐CoV‐2 infection. In addition, P4 is regarded as a potent antagonist of mineralocorticoid receptor (MR), it could reduce MRs that were activated by stimulated aldosterone from high AngII during SARS‐CoV‐2. P4 active metabolite allopregnanolone is regarded as a neurosteroid that acts as a positive modulator of γ‐aminobutyric acid (GABA A ) so it may reduce neuropsychiatric manifestations and dysautonomia in COVID‐19 patients. Conclusion : Taken together, the anti‐inflammatory and immunomodulatory properties of P4 may improve central and peripheral complications in COVID‐19.
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Multivariable logistic regression was conducted to evaluate the relationship between smoking and SARS-CoV-2 confi rmed cases, and its severity. Results: Overall, it was confi rmed that 22.6% of smokers had positive COVID-19 PCR tests compared to 42.1% of non-smokers. COVID-19 is a public health problem, and the results showed that there was a relationship between smoking and COVID-19 confi rmed cases and severity. The results showed that smoking, adjusting for other related factors, reduces the odds of COVID-19 by 58%, but increases the odds of severe disease by 89%. Conclusion: In this study, smoking was significantly associated with a low chance of developing COVID-19 disease but higher odds of severity. These significant results were reported even in the presence of under-reporting of smoking by patients, which underestimates the association. These results should not be ignored, and further studies are needed.
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Inflammation, although necessary to fight infections, becomes a threat when it exceeds the capability of the immune system to control it. In addition, inflammation is a cause and/or symptom of many different disorders, including metabolic, neurodegenerative, autoimmune and cardiovascular diseases. Comorbidities and advanced age are typical predictors of more severe cases of seasonal viral infection, with COVID-19 a clear example. The primary importance of mitogen-activated protein kinases (MAPKs) in the course of COVID-19 is evident in the mechanisms by which cells are infected with SARS-CoV-2; the cytokine storm that profoundly worsens a patient’s condition; the pathogenesis of diseases, such as diabetes, obesity, and hypertension, that contribute to a worsened prognosis; and post-COVID-19 complications, such as brain fog and thrombosis. An increasing number of reports have revealed that MAPKs are regulated by carbon dioxide (CO2); hence, we reviewed the literature to identify associations between CO2 and MAPKs and possible therapeutic benefits resulting from the elevation of CO2 levels. CO2 regulates key processes leading to and resulting from inflammation, and the therapeutic effects of CO2 (or bicarbonate, HCO3−) have been documented in all of the abovementioned comorbidities and complications of COVID-19 in which MAPKs play roles. The overlapping MAPK and CO2 signalling pathways in the contexts of allergy, apoptosis and cell survival, pulmonary oedema (alveolar fluid resorption), and mechanical ventilation–induced responses in lungs and related to mitochondria are also discussed.
Purpose: In our study, we aimed to reveal the number of applications made to the smoking cessation clinic in our hospital, smoking cessation behavior and the relationship between this situation and the status of being diagnosed with COVID-19 in the nine months before and after March 11, 2020, when the first case with a diagnosis of COVID-19 was detected in our country. Method: Individuals over 18 who applied to the Ministry of Health Ordu University Training and Research Hospital smoking cessation outpatient clinic within nine months before (Group A) and after the COVID-19 pandemic (Group B) were included in our study. Age, gender, chronic diseases, Fagerström addiction scores, and treatment they received for smoking cessation were noted through the tobacco addiction treatment monitoring system (TÜBATİS), and their smoking status was questioned by reaching them three months after their application to us. In the first year of the pandemic, the patients in Group A were reached again and questioned whether they were diagnosed with COVID-19 (PCR positivity). Results: It was determined that there were 320 patients in Group A and 60 patients in Group B, and there was a statistically significant difference in age and smoking cessation behavior between the two groups (p
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Tobacco production is one of the main activities of small farming in Southern Brazil, due its high economic value. Brazil is ranked as the second largest producer and the largest exporter in the world. The objective of this work was to apply Precision Agriculture tools, good management practices and variable rate nitrogen fertilization in Tobacco Virginia. The study was carried out in a commercial field of Virgínia tobacco cultivar in the municipality of Agudo/RS. Aerial images were carried out to obtain the MPRI, NDRE, NDVI and NDWI vegetation indexes using multispectral images from the RedEdge-Mx sensor onboard a Remotely Piloted Aircraft, and the indices were also generated with data from the FieldSpec-HH2 spectroradiometer, in various phenological stages of the tobacco. Data analysis was performed using multivariate statistics with the Factor Analysis method. The rates of nitrogen input in the experiment were adequate to obtain a range of nitrogen content in the leaves, yield and vegetation indices. The results showed that PA tools applied in tobacco crops could reduce nitrogen rates in relation to farmer business as usual, and have the potential to increase economic returns, productivity, leaf quality and net income.
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The international spread of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) poses a global challenge on both healthcare and society. A multitude of research efforts worldwide aim at characterizing the cellular factors involved in viral transmission in order to reveal therapeutic targets. For a full understanding of the susceptibility for SARS-CoV-2 infection, the cell type-specific expression of the host cell surface receptor is necessary. The key protein suggested to be involved in host cell entry is Angiotensin I converting enzyme 2 (ACE2), and its expression has been reported in various human organs, in some cases with inconsistent or contradictory results. Here, we aim to verify a reliable expression profile of ACE2 in all major human tissues and cell types. Based on stringently validated immunohistochemical analysis and high-throughput mRNA sequencing from several datasets, we found that ACE2 expression is mainly localized to microvilli of the intestinal tract and renal proximal tubules, gallbladder epithelium, testicular Sertoli cells and Leydig cells, glandular cells of seminal vesicle and cardiomyocytes. The expression in several other previously reported locations, including alveolar type II (AT2) cells, could not be confirmed. Furthermore, ACE2 expression was absent in the AT2 lung carcinoma cell line A549, often used as a model for viral replication studies. Our analysis suggests that the expression of ACE2 in the human respiratory system appears to be limited, and the expression of the receptor in lung or respiratory epithelia on the protein level is yet to be confirmed. This raises questions regarding the role of ACE2 for infection of human lungs and highlights the need to further explore the route of transmission during SARS-CoV-2 infection.
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Background: The amelioration of the current COVID pandemic relies on swift and efficient case finding as well as stringent social distancing measures. Current advice suggests that fever or new onset dry cough are the commonest presenting complaints. Methodology: We present a case report and case series as well as other evidence that there is an important fourth presenting syndrome, namely isolated sudden onset anosmia (ISOA), which should be considered highly suspicious for SARS-CoV-2. Results: A patient presenting with ISOA who went on to test positive for infection with COVID-19 and did not develop any further symptoms as well as a case series of similar patients although limited by the lack of reliable testing at the moment. Conclusions: We posit the existence of a fourth common syndrome of COVID-19 infection: isolated sudden onset anosmia (ISOA) and urge the international community to consider this presentation in current management advice.
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Although several clinical trials are now underway to test possible therapies, the worldwide response to the COVID-19 outbreak has been largely limited to monitoring/containment. We report here that Ivermectin, an FDA-approved anti-parasitic previously shown to have broad-spectrum anti-viral activity in vitro, is an inhibitor of the causative virus (SARS-CoV-2), with a single addition to Vero-hSLAM cells 2 hours post infection with SARS-CoV-2 able to effect ∼5000-fold reduction in viral RNA at 48 h. Ivermectin therefore warrants further investigation for possible benefits in humans.
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A novel and highly pathogenic coronavirus (SARS-CoV-2) has caused an outbreak in Wuhan city, Hubei province of China since December 2019, and soon spread nationwide and spilled over to other countries around the world1–3. To better understand the initial step of infection at an atomic level, we determined the crystal structure of the SARS-CoV-2 spike receptor-binding domain (RBD) bound to the cell receptor ACE2 at 2.45 Å resolution. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also utilizes ACE2 as the cell receptor⁴. Structural analysis identified residues in the SARS-CoV-2 RBD that are critical for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly argue for convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses1–3,5. The epitopes of two SARS-CoV antibodies targeting the RBD are also analysed with the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies.
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The new coronavirus, classified as SARS‐CoV‐2 that emerged in Hubei province in China, causes a new coronavirus disease, which was termed COVID‐19 by WHO on February 11, 2020. COVID‐19 claimed almost 19000 lives around the world by March 25, 2020
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The outbreak of the novel coronavirus in China (SARS-CoV-2) that began in December 2019 presents a significant and urgent threat to global health. This study was conducted to provide the international community with a deeper understanding of this new infectious disease. Epidemiological, clinical features, laboratory findings, radiological characteristics, treatment, and clinical outcomes of 135 patients in northeast Chongqing were collected and analyzed in this study. A total of 135 hospitalized patients with COVID-19 were enrolled. The median age was 47 years (interquartile range, 36-55), and there was no significant gender difference (53.3% men). The majority of patients had contact with people from the Wuhan area. Forty-three (31.9%) patients had underlying disease, primarily hypertension (13 [9.6%]), diabetes (12 [8.9%]), cardiovascular disease (7 [5.2%]), and malignancy (4 [3.0%]). Common symptoms included fever (120 [88.9%]), cough (102 [76.5%]), and fatigue (44 [32.5%]). Chest computed tomography scans showed bilateral patchy shadows or ground glass opacity in the lungs of all the patients. All patients received antiviral therapy (135 [100%]) (Kaletra and interferon were both used), antibacterial therapy (59 [43.7%]), and corticosteroids (36 [26.7%]). In addition, many patients received traditional Chinese medicine (TCM) (124 [91.8%]). It is suggested that patients should receive Kaletra early and should be treated by a combination of Western and Chinese medicines. Compared to the mild cases, the severe ones had lower lymphocyte counts and higher plasma levels of Pt, APTT, d-dimer, lactate dehydrogenase, PCT, ALB, C-reactive protein, and aspartate aminotransferase. This study demonstrates the clinic features and therapies of 135 COVID-19 patients. Kaletra and TCM played an important role in the treatment of the viral pneumonia. Further studies are required to explore the role of Kaletra and TCM in the treatment of COVID-19.
Background: Since December 2019, an outbreak of Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, and is now becoming a global threat. We aimed to delineate and compare the immunologic features of severe and moderate COVID-19. Methods: In this retrospective study, the clinical and immunologic characteristics of 21 patients (17 male and 4 female) with COVID-19 were analyzed. These patients were classified as severe (11 cases) and moderate (10 cases) according to the Guidelines released by the National Health Commission of China. Results: The median age of severe and moderate cases was 61.0 and 52.0 years, respectively. Common clinical manifestations included fever, cough and fatigue. Compared to moderate cases, severe cases more frequently had dyspnea, lymphopenia, and hypoalbuminemia, with higher levels of alanine aminotransferase, lactate dehydrogenase, C-reactive protein, ferritin and D-dimer as well as markedly higher levels of IL-2R, IL-6, IL-10, and TNF-α. Absolute number of T lymphocytes, CD4+T and CD8+T cells decreased in nearly all the patients, and were markedly lower in severe cases (294.0, 177.5 and 89.0 × 106/L) than moderate cases (640.5, 381.5 and 254.0 × 106/L). The expressions of IFN-γ by CD4+T cells tended to be lower in severe cases (14.1%) than moderate cases (22.8%). Conclusion: The SARS-CoV-2 infection may affect primarily T lymphocytes particularly CD4+T and CD8+ T cells, resulting in decrease in numbers as well as IFN-γ production. These potential immunological markers may be of importance due to their correlation with disease severity in COVID-19.
Background: Since December 2019, novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19) occurred in Wuhan, and rapidly spread throughout China. This study aimed to clarify the characteristics of patients with refractory COVID-19. Methods: In this retrospective single-center study, we included 155 consecutive patients with confirmed COVID-19 in Zhongnan Hospital of Wuhan University from January 1st to February 5th. The cases were divided into general and refractory COVID-19 groups according to the clinical efficacy after hospitalization, and the difference between groups were compared. Results: Compared with general COVID-19 patients (45.2%), refractory patients had an older age, male sex, more underlying comorbidities, lower incidence of fever, higher levels of maximum temperature among fever cases, higher incidence of breath shortness and anorexia, severer disease assessment on admission, high levels of neutrophil, aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and C-reactive protein, lower levels of platelets and albumin, and higher incidence of bilateral pneumonia and pleural effusion (P<0.05). Refractory COVID-19 patients were more likely to receive oxygen, mechanical ventilation, expectorant, and adjunctive treatment including corticosteroid, antiviral drugs and immune enhancer (P<0.05). After adjustment, those with refractory COVID-19 were also more likely to have a male sex and manifestations of anorexia and fever on admission, and receive oxygen, expectorant and adjunctive agents (P<0.05) when considering the factors of disease severity on admission, mechanical ventilation, and ICU transfer. Conclusion: Nearly 50% COVID-19 patients could not reach obvious clinical and radiological remission within 10 days after hospitalization. The patients with male sex, anorexia and no fever on admission predicted poor efficacy.