Analyzing potential correlation between smoking and COVID-19 mortality

Background:

In this analysis, I’m looking at some researches pertaining to the association between smoking and COVID-19 illness/mortality. There are number of studies ([1], [2], [3], [4]) that dig down on smoking/COVID-19 mortality relationship and found some inverse trend between smoking and COVID-19 illness/mortality (though, those studies are waiting for peer review).
Suggested mechanisms that may confer a protective effect of smoking include altered host cell expression of angiotensin-converting enzyme 2 (ACE2, the receptor the virus uses to infects cells). Experimental data pointed that infection with SARS-CoV and SARS-CoV-2 leads to down-regulation of ACE2 and this down-regulation is detrimental due to uncontrolled ACE and angiotensin 2 activity. It has been observed that decreased ACE2 availability contributes to lung injury and ARDS development. More recent analyses suggest that up-regulation of ACE-2 caused by smoking could be detrimental for COVID-19.
Therefore, higher ACE2 expression, while seemingly paradoxical, may protect against acute lung injury caused by COVID-19. Other explanations include the anti-inflammatory activity of nicotine; the antiviral effect of nitric oxide; the effects of smoking on the immune system and vapor heat-related stimulation of immunity in the respiratory tract.
The study made by University of Washington and Stanford University School of Medicine [1] shown that smokers are significantly under-represented among hospitalized COVID-19 patients in many countries where smoking population prevailed. Another study [2] conducted by Sorbonne University medical team consisted of gathering and analyzing statistics from patients hospitalized with COVD-19 in French clinics. They concluded that active smokers may be protected against symptomatic COVID-19. This was evidenced for outpatients (who have less serious infections) as well as for hospitalized patients.
The physio pathological process underlying this effect may involve nicotine through the nicotinic receptor (and not the smoke of cigarettes per se). As it was mentioned in article [4], “Since nicotine has been shown to activate the Th2 branch of the immune response, it would be interesting to test if nicotine could mediate these effects through the tilting of the Th1/Th2 immune branches towards Th2”. But all studies stressed out that any of such hypothesis deserves further evidence and findings needs careful consideration and cannot be translating into a clinical practice as it. Careful investigation of the potential protective effect of nicotine should be investigated both in in vitro and in vivo before any firm conclusion can be drawn. The interaction of smoking and COVID-19 will only be reliably determined by carefully designed prospective study, and there is reason to believe that there are unknown confounds that may be spuriously suggesting a protective effect of smoking.

Analysis and Annotations for presented Dashboard:

In my analysis I used data from worldbank.org [5] related to Smoking prevalence around the world ( i.e. percent of smokers to the entire population for each country), as well John Hopkins site (COVID-19 mortality rate). When I performed preliminary analysis I found that smoking / COVID-19 mortality correlation for all reviewed countries is not consistent and depends of the smoking rate in particular country, so I created three scenarios for different smoking rate range: 1) less than 13%; 2) between 14 and 20%, 3) more than 30%. Second scenario spans majority of reviewed countries, so in this scenario I used COVID-19 mortality rank for each country (the lowest rank is for the lowest mortality) and we can see that trend is showing positive correlation between countries COVID-19 mortality rate and their smoking rate. But first and third scenarios are showing obvious negative correlation with the R value (Pearson correlation coefficient) as -0.58 and -0.249 respectively.
To make visualization more comprehensive, I created colored areas for case with countries having minimal COVID-19 mortality rate (less than 10/per capita), but high smoking rate (more than 29%). The drop line shows that highest smoking rate contributes to the lowest mortality rate (like in Greece, Montenegro, Serbia, etc.). As in my previous dashboards, all info (i.e. country name, mortality rate, smoking rate) is available by hovering over each circle (scenarios 1 and 3), square (scenario 1) and colored areas/drop line (scenario 4), as well as trend lines to see statistics.
References:
1. National Smoking Rates Correlate Inversely with COVID-19 Mortality
2. Low rate of daily active tobacco smoking in patients with symptomatic COVID-19
3. Smoking, vaping and hospitalization for COVID-19
4. Review of: Low incidence of daily active tobacco smoking in patients with symptomatic COVID-19
5. Smoking prevalence, total (ages 15+)p