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.