Association Between Smoking and SARS-CoV-2 Infection: Cross-sectional Study of the EPICOVID19 Internet-Based Survey.

BACKGROUND: Several studies have reported a low prevalence of current smoking among hospitalized COVID-19 cases; however, no definitive conclusions can be drawn. OBJECTIVE: We investigated the association of tobacco smoke exposure with nasopharyngeal swab (NPS) test results for SARS-CoV-2 infection and disease severity accounting for possible confounders. METHODS: The nationwide, self-administered, cross-sectional web-based Italian National Epidemiological Survey on COVID-19 (EPICOVID19) was administered to an Italian population of 198,822 adult volunteers who filled in an online questionnaire between April 13 and June 2, 2020. For this study, we analyzed 6857 individuals with known NPS test results. The associations of smoking status and the dose-response relationship with a positive NPS test result and infection severity were calculated as odds ratios (ORs) with 95% CIs by means of logistic and multinomial regression models adjusting for sociodemographic, clinical, and behavioral characteristics. RESULTS: Out of the 6857 individuals (mean age 47.9 years, SD 14.1; 4516/6857, 65.9% female), 63.2% (4334/6857) had never smoked, 21.3% (1463/6857) were former smokers, and 15.5% (1060/6857) were current smokers. Compared to nonsmokers, current smokers were younger, were more educated, were less affected by chronic diseases, reported COVID-19-like symptoms less frequently, were less frequently hospitalized, and less frequently tested positive for COVID-19. In multivariate analysis, current smokers had almost half the odds of a positive NPS test result (OR 0.54, 95% CI 0.45-0.65) compared to nonsmokers. We also found a dose-dependent relationship with tobacco smoke: mild smokers (adjusted OR [aOR] 0.76, 95% CI 0.55-1.05), moderate smokers (aOR 0.56, 95% CI 0.42-0.73), and heavy smokers (aOR 0.38, 95% CI 0.27-0.53). This inverse association also persisted when considering the severity of the infection. Current smokers had a statistically significantly lower probability of having asymptomatic (aOR 0.50, 95% CI 0.27-0.92), mild (aOR 0.65, 95% CI 0.53-0.81), and severe infections (aOR 0.27, 95% CI 0.17-0.42) compared to those who never smoked. CONCLUSIONS: Current smoking was negatively associated with SARS-CoV-2 infection with a dose-dependent relationship. Ad hoc experimental studies are needed to elucidate the mechanisms underlying this association. TRIAL REGISTRATION: ClinicalTrials.gov NCT04471701; https://clinicaltrials.gov/ct2/show/NCT04471701.

Sex- and gender-related differences linked to SARS-CoV-2 infection among the participants in the web-based EPICOVID19 survey: the hormonal hypothesis.

Objective To investigate sex- and gender-based differences linked to SARS-COV-2 infection and to explore the role of hormonal therapy (HT) in females. Study design Data from the self-administered, cross-sectional, web-based EPICOVID19 survey of 198,822 adults living in Italy who completed an online questionnaire during the first wave of the epidemic in Italy (April-May 2020) were analyzed. Main outcomes measures Multivariate binary logistic and multinomial regression models were respectively used to estimate the odds ratios (ORs) with 95% confidence intervals (CIs) for positive nasopharyngeal swab (NPS) test results and severe SARS-CoV-2 infection. Results The data from 6,873 participants (mean age 47.9 ± 14.1 years, 65.8% females) who had a known result from an NPS test were analyzed. According to the multivariate analysis, females had lower odds of a positive result from the NPS test (aOR 0.75, 95%CI 0.66-0.85) and of having a severe infection (aOR 0.46, 95%CI 0.37-0.57) than did their male counterparts. These differences were greater with decreasing age in both sexes. In addition, females aged ≥60 years receiving HT (N = 2,153, 47.6%) had a 46% lower probability of having a positive NPS test (aOR 0.54, 95%CI 0.36-0.80) than their same-aged peers who had never used HT; there were no differences in the younger age groups with respect to HT status. Conclusion Female sex was associated with an age-dependent lower risk of having a severe SARS-CoV-2 infection than their male counterparts. Age seemed to modify the relationship between HT status and infection: while the two were not related among younger participants, it was negative in the older ones. Future prospective studies are needed to elucidate the potential protective role sex hormones may play. Trial registration ClinicalTrials.gov NCT04471701.

The Association between Influenza and Pneumococcal Vaccinations and SARS-Cov-2 Infection: Data from the EPICOVID19 Web-Based Survey.

The present study aims to evaluate whether influenza and pneumococcal vaccinations are associated with positive nasopharyngeal swab (NPS) testing to detect SARS-CoV-2. Data from the Italian cross-sectional web-based survey (EPICOVID19), based on a self-selection sample of individuals aged ≥18, were considered. The probability of a positive SARS-CoV-2 NPS test result as a function of influenza or anti-pneumococcal vaccination was evaluated using multivariable logistic regression, stratifying analysis by age (<65 years, ≥65 years). From April 2020, 170,731 individuals aged <65 years and 28,097 ≥65 years filled out the EPICOVID19 questionnaire. Influenza and anti-pneumococcal vaccinations were received, respectively, by 16% and 2% of those <65 years, and by 53% and 13% of those ≥65 years. SARS-CoV-2 NPS testing was reported by 6680 participants. Anti-pneumococcal and influenza vaccinations were associated with a decreased probability of a SARS-CoV-2 NPS positive test in the younger participants (OR = 0.61, 95% CI 0.41-0.91; OR = 0.85, 95%CI 0.74-0.98; respectively). A significantly lower probability of a positive test result was detected in the individuals ≥65 years who received anti-pneumococcal vaccination (OR = 0.56, 95%CI 0.33-0.95). These results need to be confirmed by further investigations, but they are relevant given the probable coexistence of influenza, bacterial infections, and COVID-19 over the coming autumn-winter season.

Self-Reported Symptoms of SARS-CoV-2 Infection in a Nonhospitalized Population in Italy: Cross-Sectional Study of the EPICOVID19 Web-Based Survey.

BACKGROUND: Understanding the occurrence of symptoms resembling those of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a large nonhospitalized population at the peak of the epidemic in Italy is of paramount importance; however, data are currently scarce. OBJECTIVE: The aims of this study were to evaluate the association of self-reported symptoms with SARS-CoV-2 nasopharyngeal swab (NPS) test results in nonhospitalized individuals and to estimate the occurrence of symptoms associated with coronavirus disease (COVID-19) in a larger nontested population. METHODS: EPICOVID19 is a self-administered cross-sectional voluntary web-based survey of adults throughout Italy who completed an anonymous questionnaire in the period of April 13 to 21, 2020. The associations between symptoms potentially related to SARS-CoV-2 infection and NPS results were calculated as adjusted odds ratios (aORs) with 95% CIs by multiple logistic regression analysis controlling for age, sex, education, smoking habits, and number of comorbidities. Thereafter, for each symptom and for combinations of the symptoms, we calculated the sensitivity, specificity, accuracy, and areas under the curve (AUCs) in a receiver operating characteristic (ROC) analysis to estimate the occurrence of COVID-19-like infection in the nontested population. RESULTS: A total of 171,310 people responded to the survey, of whom 102,543 (59.9%) were women; mean age 47.4 years. Out of the 4785 respondents with known NPS test results, 4392 were not hospitalized. Among the 4392 nonhospitalized respondents, those with positive NPS tests (856, 19.5%) most frequently reported myalgia (527, 61.6%), olfactory and taste disorders (507, 59.2%), cough (466, 54.4%), and fever (444, 51.9%), whereas 7.7% were asymptomatic. Multiple regression analysis showed that olfactory and taste disorders (aOR 10.3, 95% CI 8.4-12.7), fever (aOR 2.5, 95% CI 2.0-3.1), myalgia (aOR 1.5, 95% CI 1.2-1.8), and cough (aOR 1.3, 95% CI 1.0-1.6) were associated with NPS positivity. Having two to four of these symptoms increased the aOR from 7.4 (95% CI 5.6-9.7) to 35.5 (95% CI 24.6-52.2). The combination of the four symptoms showed an AUC of 0.810 (95% CI 0.795-0.825) in classifying positive NPS test results and then was applied to the nonhospitalized and nontested sample (n=165,782). We found that 7739 to 20,103 of these 165,782 respondents (4.4% to 12.1%) had experienced symptoms suggestive of COVID-19 infection. CONCLUSIONS: Our results suggest that self-reported symptoms are reliable indicators of SARS-CoV-2 infection in a pandemic context. A nonnegligible number of symptomatic respondents (up to 12.1%) were undiagnosed and potentially contributed to the spread of the infection. TRIAL REGISTRATION: ClinicalTrials.gov NCT04471701; https://clinicaltrials.gov/ct2/show/NCT04471701.