Discussion:
SARS-CoV-2 infection continues to be an urgent public health challenge
in China and throughout the world. Most infected patients have mild
illness and completely recover after two weeks. However, once infected
patients progress to severe illness with acute respiratory distress
syndrome, over 10% of them worsen in a short period of time and
die3. As the pathogenesis of SARS-CoV-2 infection is
unknown, there is no standard specific treatment and most patients
receive symptomatic treatment. Thus, a further understanding of the
pathogenesis and treatment of the disease is urgently needed. In Figure
1, we see effects of variable changes on dead and living groups.
Previous studies have found that some routine laboratory biomarkers are
out of reference ranges and are higher in more severe
disease11. In accordance with those studies, we also
found that some biomarkers, such as lactate dehydrogenase, troponin and
D-dimer, were higher in cases of severe illness, but these biomarkers
were not all specific to SARS-CoV-2. Similar to other viral infections,
neutrophils showed no obvious change in mild cases, while inflammatory
biomarkers such as CRP were increased.
There is a small amount of research that says that smoking could
increase the risk of COVID-19 via upregulation of ACE-2 expression, a
known cellular entry gateway for SARS-CoV-2 (7,8). However, there are a
few inconsistencies with this hypothesis. First of all, the spike
protein of the virus is responsible for ACE-2 binding, and it requires
its counterpart to be localized on the plasma membrane in order to be
subsequently internalized12,13. Therefore, the gene
expression does not conclusively indicate increased viral infection
risk. Second, it is known that ACE-2 expression is downregulated on
plasma membranes following SARS-CoV-2 infection because of
internalization of ACE-2-virus samples14. Third,
simple ACE-2 expression on plasma membranes may not be an important
element in establishment of a potential risk factor for virus infection.
In fact, once the spike protein is bound to ACE-2, the cell is required
to trigger a complex series of biochemical activities and molecular
signals in order to internalize the virus12. The view
that overexpression of ACE2 is harmful does not take into account more
recent evidence that upregulation of ACE2 may in fact be protective
against disease severity9. Experimental data suggests
that infection with SARS-CoV-2 leads to downregulation of ACE2, and this
downregulation is harmful because of uncontrolled ACE and angiotensin II
activity8,9. It has been observed that decreased ACE2
availability contributes to lung injury and increases the risk of ARDS
development9,15. Therefore, higher ACE2 expression,
while it seems paradoxical, may protect against the acute lung injury
caused by COVID-1916.
In our study, we saw smaller-than-expected smoking rates in hospitalized
patients who tested positive for COVID-19. That statistic catalyzed this
study. We performed our study with inpatients because their progress was
easy to follow and similar studies were performed in hospitalized
patients.
14 of the patients in the study were smokers (6.5%). In the latest
studies on the prevalence of smoking in Turkey, the nationwide rate of
smoking was 25.7%17. One in four people in Turkey is
a smoker, while in COVID-19 isolation service only a 6.5% rate of
smoking was observed. That supports the theory that smoking hasn’t
negative impact on COVID-19 development. In the review showing the
relationship between smoking and COVID-19 in China, where the smoking
prevalence is 26.6%, 5960 patients’ smoking rates have changed between
1.4-12.6%. This study, conducted with patients hospitalized in COVID-19
isolation service, claimed that smoking did not meet the hospitalization
criteria for COVID-19, and on the contrary, it may reduce risk. The
results of our study are similar to and supportive of these results. At
the same time, the CT scores we used to stage the severity of the
disease were not statistically related to smoking (p-value: 0.368121).
We did not see any significant effect of smoking on mortality rate
(p-value: 0.2777) or on discharge time (p-value: 0.2496).
A semi-quantitative scoring obtained from CT images was used to
determine the severity of COVID-19’s pulmonary involvement. A CT scan
was performed during the first day of the patient’s hospitalization.
Each lung lobe was scored as 0 (0%), 1 (1–25%), 2 (26–50%), 3
(51–75%), or 4 (76–100%), according to the COVID-19 involvement
percentage. The total involvement score of 5 lobes (0–20) was obtained,
and a CT evaluation was performed in the lung parenchyma window. Scoring
was performed according to the ground glass opacity appearance of
COVID-19, which is the typical lung involvement, and according to the
percentage of consolidations. In CT imaging with a staging of maximum 4
and minimum 0 points, the mean value was 1.95.
The average radiological stage was reported as 2.56 in the dead
patients’ group. There was a correlation between the radiological
predictor and the outcome status (p-value: 0.002). It seems that an
elevated radiological stage is a predictor of death.
We do not have a standard discharge time at our hospital. When the
patients show no fever, no respiratory distress, normalized laboratory
tests and good general condition for at least for three days, we
discharge them. The average discharge time was 13.8 days. According to
our data, we can calculate the average discharge time by scoring their
CTs. A high point CT stage will likely delay discharge (p-value:
0.0049).
In conclusion, observation of a consistently low prevalence of smoking
among hospitalized COVID-19 cases, together with the potential
mechanisms through which nicotine interacts with the inflammatory
process and the renin–angiotensin–aldosterone system, highlights that
the relationship between smoking and COVID-19 should be further
investigated. The complex interaction between smoking and the
renin-angiotensin-aldosterone/ACE-2 systems present multiple challenges
to the researcher, the clinician, and the COVID-19 patient. However, CT
staging appears to be a very important prognostic factor that may be
helpful in the future, especially regarding death and discharge times.
The shortcomings of our study are that our most recent information about
current cigarette prevalence in Turkey is from 2014, our patient numbers
are low, and we do not have any data on electronic cigarette usage
versus traditional heat-based cigarette usage.