Cross-Immunity as a Potential Explanation for the Smoker's Paradox in COVID-19: Evidence from a Systematic Review and Meta-Analysis

Abstract Introduction: Recent evidence shows that a cross-immunity reaction exists between the T-cells associated with common cold coronaviruses (229E, NL63, OC43, HKU1) and SARS-CoV-2, the causal agent of COVID-19. 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. 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. Methods: 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. Results: 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). Conclusions: Our data suggest that COVID-19 might be less prevalent among smokers due to greater cross-inmmunity 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