COVID-19, a disease of the nicotinic cholinergic system? Nicotine may be protective

Corona Virus Disease 2019 (COVID-19) is a disease caused by a novel coronavirus, SARS-CoV-2. On 23 March, we presented for the first time evidence of a low prevalence of smoking among hospitalized patients with COVID-19 in China. On 3 April, we were the first to establish the hypothesis that nicotine may be beneficial for COVID-19 patients and should be evaluated in clinical trials due to its anti-inflammatory properties. We present briefly the hypothesis that COVID-19 could be a disease of the nicotinic cholinergic system. Additionally we emphasize that researchers should be cautious when presenting previously-published (or pre-published) work as their own "novel" work. Copying methodologies and reporting previously-presented hypotheses without citing the original authors, especially when publication and pre-publication dates are documented, can be considered plagiarism and a breach of intellectual property copyright.

E-cigarette use and COVID-19 in youth and young adults: serious questions about data reliability and call for retraction

In a recent study, Gaiha et al. examined the association between e-cigarette use and COVID-19 in an online cross-sectional study of people aged 13-24 years conducted from May 6 to May 14, 2020. We have noticed serious issues in population weighting, response bias and biological implausibility. The suggested conclusions and interpretation of the study findings cannot be considered reliable. These issues raise the question of retracting the study.

Smoking, vaping and hospitalization for COVID-19

The study presents an analysis of the current smoking prevalence among hospitalized patients with COVID-19 in China, compared to the population smoking prevalence in China (52.1% in males and 2.7% in females). We identified 6 studies examining the clinical characteristics of hospitalized COVID-19 patients that presented data on the smoking status. The expected number of smokers was calculated using the formula Expected smokers = (males x 0.521) (females x 0.027). An unusually low prevalence of current smoking was observed among hospitalized COVID-19 patients (9.6%, 95%CI: 8.2-11.1%) compared to the expected prevalence based on smoking prevalence in China (31.2%, 95%CI: 29.0-33.4%;z-statistic: 19.16, P < 0.0001). This preliminary analysis does not support the argument that current smoking is a risk factor for hospitalization for COVID-19, and might suggest a protective role. The latter could be linked to the downregulation of ACE2 expression that has been previously known to be induced by smoking. No studies recording e-cigarette use status among hospitalized COVID-19 patients were identified. Thus, no recommendation can be made for e-cigarette users. Keywords. SARS-CoV-2, COVID-19, ACE2, expression, susceptibility, smoking, hospitalization, electronic cigarette.

Smoking prevalence among hospitalized COVID-19 patients and its association with disease severity and mortality: an expanded re-analysis of a recent publication.

BACKGROUND: There is a lot of debate about the effects of smoking on COVID-19. A recent fixed-effects meta-analysis found smoking to be associated with disease severity among hospitalized patients, but other studies report an unusually low prevalence of smoking among hospitalized patients. The purpose of this study was to expand the analysis by calculating the prevalence odds ratio (POR) of smoking among hospitalized COVID-19 patients, while the association between smoking and disease severity and mortality was examined by random-effects meta-analyses considering the highly heterogeneous study populations. METHODS: The same studies as examined in the previous meta-analysis were analyzed (N = 22, 20 studies from China and 2 from USA). The POR relative to the expected smoking prevalence was calculated using gender and age-adjusted population smoking rates. Random-effects meta-analyses were used for all other associations. RESULTS: A total of 7162 patients were included, with 482 being smokers. The POR was 0.24 (95%CI 0.19-0.30). Unlike the original study, the association between smoking and disease severity was not statistically significant using random-effects meta-analysis (OR 1.40, 95%CI 0.98-1.98). In agreement with the original study, no statistically significant association was found between smoking and mortality (OR 1.86, 95%CI 0.88-3.94). CONCLUSION: An unusually low prevalence of smoking, approximately 1/4th the expected prevalence, was observed among hospitalized COVID-19 patients. Any association between smoking and COVID-19 severity cannot be generalized but should refer to the seemingly low proportion of smokers who develop severe COVID-19 that requires hospitalization. Smokers should be advised to quit due to long-term health risks, but pharmaceutical nicotine or other nicotinic cholinergic agonists should be explored as potential therapeutic options, based on a recently presented hypothesis.

Current smoking, former smoking, and adverse outcome among hospitalized COVID-19 patients: a systematic review and meta-analysis.

BACKGROUND: The purpose of this study was to examine the prevalence and effects of current smoking on adverse outcomes among hospitalized COVID-19 patients. METHODS: A systematic review of the literature (PubMed) identified 18 (from a total of 1398) relevant studies. Pooled current smoking prevalence was compared with the gender-adjusted and gender and age-adjusted, population-based expected prevalence by calculating prevalence odds ratio (POR). The association between current, compared with non-current and former, smoking and adverse outcome was examined. A secondary analysis was performed by including 12 pre-publications (30 studies in total). All analyses were performed using random-effects meta-analysis. RESULTS: Among 6515 patients, the pooled prevalence of current smoking was 6.8% [95% confidence interval (CI): 4.8-9.1%]. The gender-adjusted POR was 0.20 (95% CI: 0.16-0.25, p < 0.001), and the gender and age-adjusted POR was 0.24 (95% CI: 0.19-0.30, p < 0.001). Current smokers were more likely to have an adverse outcome compared with non-current smokers [odds ratio (OR): 1.53, 95%CI: 1.06-2.20, p = 0.022] but less likely compared with former smokers (OR: 0.42, 95% CI: 0.27-0.74, p = 0.003). When pre-publications were added (n = 10,631), the gender-adjusted POR was 0.27 (95% CI: 0.19-0.38, p < 0.001) and the gender and age-adjusted POR was 0.34 (95% CI: 0.24-0.48, p < 0.001). CONCLUSION: This meta-analysis of retrospective observational case series found an unexpectedly low prevalence of current smoking among hospitalized patients with COVID-19. Hospitalized current smokers had higher odds compared with non-current smokers but lower odds compared with former smokers for an adverse outcome. Smoking cannot be considered a protective measure for COVID-19. However, the hypothesis that nicotine may have a protective effect in COVID-19 that is partially masked by smoking-related toxicity and by the abrupt cessation of nicotine intake when smokers are hospitalized should be explored in laboratory studies and clinical trials using pharmaceutical nicotine products.

Systematic review of the prevalence of current smoking among hospitalized COVID-19 patients in China: could nicotine be a therapeutic option?

The effects of smoking on Corona Virus Disease 2019 (COVID-19) are currently unknown. The purpose of this study was to systematically examine the prevalence of current smoking among hospitalized patients with COVID-19 in China, considering the high-population smoking prevalence in China (26.6%). A systematic review of the literature (PubMed) was performed on April 1. Thirteen studies examining the clinical characteristics of hospitalized COVID-19 patients in China and presenting data on the smoking status were found. The pooled prevalence of current smoking from all studies was calculated by random-effect meta-analysis. To address the possibility that some smokers had quit shortly before hospitalization and were classified as former smokers on admission to the hospital, we performed a secondary analysis in which all former smokers were classified as current smokers. A total of 5960 patients were included in the studies identified. The current smoking prevalence ranged from 1.4% (95% CI 0.0-3.4%) to 12.6% (95% CI 10.6-14.6%). An unusually low prevalence of current smoking was observed from the pooled analysis (6.5%, 95% CI 4.9-8.2%) as compared to population smoking prevalence in China. The secondary analysis, classifying former smokers as current smokers, found a pooled estimate of 7.3% (95% CI 5.7-8.9%). In conclusion, an unexpectedly low prevalence of current smoking was observed among patients with COVID-19 in China, which was approximately 1/4th the population smoking prevalence. Although the generalized advice to quit smoking as a measure to reduce health risk remains valid, the findings, together with the well-established immunomodulatory effects of nicotine, suggest that pharmaceutical nicotine should be considered as a potential treatment option in COVID-19.