Systematic review and meta analysis of cross immunity and the smokers paradox in COVID19

COVID-19 pandemic, caused by the novel SARS-CoV-2 virus, has raised significant interest in understanding potential cross-immunity mechanisms. Recent evidence suggests that T-cells associated with common cold coronaviruses (229E, NL63, OC43, HKU1) may provide some level of cross-immunity against SARS-CoV-2. It is also known that the prevalence of smokers among patients admitted to hospital for COVID-19 is lower than expected according to the corresponding country's smoking prevalence, which is known as smoker's paradox in COVID-19. No clear consensus to explain it has yet been reached. This phenomenon suggests a complex interaction between smoking and immune response. Nonetheless, very few works have studied the prevalence of smokers in those infected by common cold coronaviruses, and its relation to COVID-19 has not been investigated. We performed a systematic review and meta-analysis to study the prevalence of smokers among patients infected by common cold coronaviruses, and to compare them to the corresponding country's smoking prevalence. L'Abbé plots were used to visually assess the consistency of the observed effects across the different studies included in the meta-analysis. Additionally, significant differences were found in smoking prevalence among the various types of ccCoV, indicating the need for further research into the biological mechanisms driving these disparities. The results show that smoking prevalence is higher among those patients infected by these coronaviruses than in the general population (OR = 1.37, 95% CI: 0.81-2.33). A study was separately done for the four coronavirus types, and the prevalence of smokers was higher in three of the four than that corresponding to country, gender and study year: OC43 (OR = 1.93, 95% CI: 0.64-5.82); HKU1 (OR = 3.62, 95% CI: 1.21-10.85); NL63 (OR = 1.93, 95% CI: 0.64-5.82); 229E (OR = 0.97, 95% CI: 0.50-1.90). The heterogeneity of the studies was assessed using the Cochrane Chi-squared test, I-squared (I2), and Tau-squared (τ2). This detailed statistical analysis enhances the robustness of our findings and highlights the variations in smoking prevalence among different ccCoVs. Our data suggest that COVID-19 might be less prevalent among smokers due to greater cross-immunity from a larger number or more recent infections by common cold coronaviruses than the non-smoking population, which would explain smoker's paradox in COVID-19. IMPLICATIONS. The low prevalence of current smokers among SARS-CoV-2 patients is a finding recurrently repeated, even leading to postulate the "smoker's paradox" in COVID-19. This fact compelled us to study the prevalence of smokers among patients infected by common cold coronaviruses, and to compare them to the corresponding country's smoking prevalence. Our data could explain smoker's paradox in COVID-19 by a greater cross immunity due to a larger number, or more recent infections by common cold coronaviruses than the non-smoking population. This manuscript allow understand potential unrevealed mechanism for low prevalence of current smokers among SARS-CoV-2 patients.