Müllerian anomalies and endometriosis as potential explanatory models for the retrograde menstruation/implantation and the embryonic remnants/celomic metaplasia pathogenic theories: a systematic review and meta-analysis.

STUDY QUESTION: Does endometriosis prevalence differ in patients with obstructive Müllerian anomalies (OMA) versus those with nonobstructive Müllerian anomalies (NOMA), and in patients with NOMA versus those without Müllerian anomalies? SUMMARY ANSWER: The quantitative synthesis of published data demonstrates a substantially increased prevalence of endometriosis in patients with OMA compared with those with NOMA, and a similar prevalence in patients with NOMA and those without Müllerian anomalies. WHAT IS KNOWN ALREADY: The pathogenesis of endometriosis has not been definitively clarified yet. A higher prevalence of endometriosis in patients with OMA than in those with NOMA would support the retrograde menstruation (RM)/implantation theory, whereas a higher prevalence of endometriosis in the NOMA group than in the group without Müllerian anomalies would support the embryonic remnants/celomic metaplasia hypothesis. STUDY DESIGN, SIZE, DURATION: This systematic review with meta-analysis was restricted to full-length, English-language articles published in peer-reviewed journals between 1980 and 2023. The PubMed and EMBASE databases were searched using the keyword 'endometriosis' in combination with 'Müllerian anomalies', 'obstructive Müllerian anomalies', 'female genital malformations', 'retrograde menstruation', 'infertility', 'pelvic pain', and 'classification'. References from relevant publications were screened, and PubMed's 'similar articles' and 'cited by' functions were used. PARTICIPANTS/MATERIALS, SETTING, METHODS: Studies were selected if they reported the prevalence of surgically confirmed endometriosis in either individuals with OMA compared to those with NOMA, or patients with NOMA compared to those without Müllerian anomalies. Cohort and case-control studies and case series were deemed eligible for inclusion. Noncomparative studies, studies not reporting both the number of individuals with endometriosis and the total number of those with Müllerian anomalies or with other gynecological conditions, those including exclusively data on patients with absent or uncertain menstrual function (e.g. complete Müllerian agenesis category), or with imperforate hymen were excluded. Two reviewers independently abstracted data. The risk of bias was assessed with the Risk of Bias In Non-randomized Studies of Exposures tool. The overall certainty of the evidence was graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. MAIN RESULTS AND THE ROLE OF CHANCE: Seven retrospective studies were included. The overall mean estimate of endometriosis prevalence was 47% (95% CI, 36-58%) in patients with OMA, and 19% (95% CI, 15-24%) in patients with NOMA, with a common odds ratio (OR) of 4.72 (95% CI, 2.54-8.77). The overall mean estimate of endometriosis prevalence in patients with NOMA was 23% (95% CI, 20-27%), and that in patients without Müllerian anomalies was 21% (95% CI, 20-22%), with a common OR of 0.95 (95% CI, 0.57-1.58). The overall certainty of the evidence according to GRADE guidelines was judged as low for both comparisons. LIMITATIONS, REASON FOR CAUTION: Some NOMA subtypes may create a partial obstacle to menstrual efflux and/or generate dysfunctional myometrial contractions that favor transtubal reflux, thus increasing the risk of endometriosis and limiting the difference between OMA and NOMA. As infertility and pelvic pain are strongly associated with endometriosis, women with these symptoms are inappropriate controls. Confounding by indication could explain the lack of difference in endometriosis prevalence between patients with NOMA and those without Müllerian anomalies. WIDER IMPLICATIONS OF THE FINDINGS: The results of this meta-analysis support the validity of the RM theory but do not definitively rule out alternative hypotheses. Thus, RM may be considered the initiator for the development of endometriotic lesions, while not excluding the contribution of both inheritable and tissue-specific genetic and epigenetic modifications as disease-promoting factors. STUDY FUNDING/COMPETING INTEREST(S): No funding was received for this review. P.Ve. is a member of the Editorial Board of Human Reproduction Open, the Journal of Obstetrics and Gynaecology Canada, and the International Editorial Board of Acta Obstetricia et Gynecologica Scandinavica; has received royalties from Wolters Kluwer for chapters on endometriosis management in the clinical decision support resource UpToDate; and maintains both a public and private gynecological practice. E.S. discloses payments from Ferring for research grants and honoraria from Merck-Serono for lectures. All other authors declare they have no conflict of interest. REGISTRATION NUMBER: N/A.

Epidemiology of acute lymphoblastic leukaemia in Sardinia, Italy: Age, sex, and environmental correlates.

Using a database of 1974-2003 incident cases of haematological malignancies, we explored the time trend, geographic spread and socio-economic and environmental correlates of ALL incidence in Sardinia, Italy, by sex and age. The age- and sex-standardized (World population) ALL incidence rate was 2.0 per 100,000 (95% CI 1.8 - 2.1) and showed variable trend patterns by sex and age. In the total population, ALL incidence showed an annual per cent change of -1.4% (95% CI -0.59 - -3.34) over the study period, with a knot separating a downward slope in 1974-1996 from an increase in 1996-2003. ALL incidence replicated such pattern in women but not men, whose incidence did not substantially vary over the study period (APC = -2.57%, 95% CI -5.45 - 0.26). Among women, the spatial analysis suggested a clustering of ALL in the southwestern part of the region, whilst only a commune had a high posterior probability of a high ALL incidence among men. Three unrelated communes showed a high posterior probability of ALL at age ≤ 24; only the most populated urban centre showed excess cases at age ≥ 25 years. There was no correlation between the geographic spread of ALL at ages ≤ 24 and ≥ 25 years (p = 0.082). Urban residence was a risk factor for the younger age group. Residences near industrial settlements and in the most populated urban centre were risk factors for subjects aged ≥ 25 years. Our findings suggest age-related differences in ALL aetiology.

A cluster randomised controlled trial to reduce respiratory effects of cotton dust exposure among textile workers: the MultiTex RCT study.

BACKGROUND: We determined the effectiveness of an intervention to reduce cotton dust-related respiratory symptoms and improve lung function of textile workers. METHODS: We undertook a cluster randomised controlled trial at 38 textile mills in Karachi, Pakistan. The intervention comprised: training in occupational health for workers and managers, formation of workplace committees to promote a health and safety plan that included wet mopping and safe disposal of cotton dust, provision of simple face masks, and further publicity about the risks from cotton dust. Participating mills were randomised following baseline data collection. The impact of the intervention was measured through surveys at 3, 12 and 18 months using questionnaires, spirometry and dust measurements. The primary outcomes were 1) changes in prevalence of a composite respiratory symptom variable, 2) changes in post-bronchodilator percentage predicted forced expiratory volume in 1 s (FEV1) and 3) changes in cotton dust levels. These were assessed using two-level mixed effects linear and logistic regression. RESULTS: Of 2031 participants recruited at baseline, 807 (40%) were available at the third follow-up. At that point, workers in the intervention arm were more likely to report an improvement in respiratory symptoms (OR 1.58, 95% CI 1.06-2.36) and lung function (FEV1 % pred: ß 1.31%, 95% CI 0.04-2.57%). Personal dust levels decreased, more so in intervention mills, although we did not observe this in adjusted models due to the small number of samples. CONCLUSION: We found the intervention to be effective in improving the respiratory health of textile workers and recommend scaling-up of such simple and feasible interventions in low- and middle-income countries.

Systematic Violence Monitoring to Reduce Underreporting and to Better Inform Workplace Violence Prevention Among Health Care Workers: Before-and-After Prospective Study.

BACKGROUND: Monitoring workplace violence (WPV) against health care workers (HCWs) through incident reporting is crucial to drive prevention, but the actual implementation is spotty and experiences underreporting. OBJECTIVE: This study aims to introduce a systematic WPV surveillance in 2 public referral hospitals in Italy and assess underreporting, WPV annual rates, and attributes "before" (2016-2020) and "after" its implementation (November 2021 to 2022). METHODS: During 2016-2020, incident reporting was based on procedures and data collection forms that were neither standardized between hospitals nor specific for aggressions. We planned and implemented a standardized WPV surveillance based on (1) an incident report form for immediate and systematic event notification, adopting international standards for violence definitions; (2) second-level root cause analysis with a dedicated psychologist, assessing violence determinants and impacts and offering psychological counseling; (3) a web-based platform for centralized data collection; and (4) periodic training for workforce coordinators and newly hired workers. We used data from incident reports to estimate underreporting, defined as an observed-to-expected (from literature and the "before" period) WPV ratio less than 1, and the 12-month WPV rates (per 100 HCWs) in the "before" and "after" periods. During the latter period, we separately estimated WPV rates for first and recurrent events. RESULTS: In the "before" period, the yearly observed-to-expected ratios were consistently below 1 and as low as 0.27, suggesting substantial violence underreporting of up to 73%. WPV annual rates declined in 1 hospital (from 1.92 in 2016 to 0.57 in 2020) and rose in the other (from 0.52 to 1.0), with the divergence being attributable to trends in underreporting. Available data were poorly informative to identify at-risk HCW subgroups. In the "after" period, the observed-to-expected ratio rose to 1.14 compared to literature and 1.91 compared to the "before" period, consistently in both hospitals. The 12-month WPV rate was 2.08 (95% CI 1.79-2.42; 1.52 and 2.35 in the 2 hospitals); one-fifth (0.41/2.08, 19.7%) was due to recurrences. Among HCWs, the youngest group (3.79; P<.001), nurses (3.19; P<.001), and male HCWs (2.62; P=.008) reported the highest rates. Emergency departments and psychiatric wards were the 2 areas at increased risk. Physical assaults were more likely in male than female HWCs (45/67, 67.2% vs 62/130, 47.7%; P=.01), but the latter experienced more mental health consequences (46/130, 35.4% vs 13/67, 19.4%; P=.02). Overall, 40.8% (53/130) of female HWCs recognized sociocultural (eg, linguistic or cultural) barriers as contributing factors for the aggression, and 30.8% (40/130) of WPV against female HCWs involved visitors as perpetrators. CONCLUSIONS: A systematic WPV surveillance reduced underreporting. The identification of high-risk workers and characterization of violence patterns and attributes can better inform priorities and contents of preventive policies. Our evaluation provides useful information for the large-scale implementation of standardized WPV-monitoring programs.

Incidence and Bayesian Mapping of Myeloid Hematologic Malignancies in Sardinia, Italy.

BACKGROUND: The epidemiology of myeloid hematologic malignancies in Italy has been poorly investigated. METHODS: We used a validated database of 1974-2003 incident cases of hematologic malignancies among the resident population (all ages) of Sardinia, Italy, to describe the incidence of myeloid malignancies overall (N = 4389 cases) and by subtype. We investigated the time trend of acute myeloid leukemia (N = 1227 cases), chronic myeloid leukemia (N = 613 cases), and myelodysplastic syndrome (N = 1296 cases), and used Bayesian methods to explore their geographic spread, and Poisson regression analysis to estimate their association with environmental and socio-economic factors. RESULTS: The annual standardized (world population) incidence rate (IR) of myeloid malignancies over the study period was 6.5 per 100,000 (95% CI 6.2-6.7). Myelodysplastic syndromes were the most prevalent subgroup (IR = 1.7, 95% CI 1.5-1.8). Incidence of all myeloid malignancies combined increased sharply during the study period with an annual percent change (APC) of 10.06% (95% CI 9.51-10.61), 19.77% for myelodysplastic syndromes (95% CI 19.63-19.91), and 3.18% (95% CI 2.99-3.37) for acute myeloid leukemia. Chronic myeloid leukemia did not show an upward trend. Apart from sporadic excesses in small rural communities and the major urban area, there was no evidence of spatial clustering. The risk of myeloid malignancies increased with increasing prevalence of sheep breeding. CONCLUSIONS: Our results might prompt further research on the local genetic and environmental determinants of myeloid hematologic malignancies.

Is a Good Sleep on Mosquito-Free Nights Worth the Risk of Lymphoma Associated with the Use of Household Insecticides? A Case-Control Study of Lymphoma Subtypes in Adults.

BACKGROUND: The evidence linking the use of household pesticides and the risk of lymphoma is scanty. METHODS: We explored the hypothesis in a population-based case-control study on lymphoma conducted in Sardinia, Italy, in 1998-2004, including 325 cases and 465 population controls and data on lifetime frequency, seasonality, and years of use of household insecticides and potential confounders. We calculated the risk of lymphoma (all subtypes) and its major subtypes associated with using household insecticides in three time windows (up to 1978, from 1979-2001, and 2002 onwards) with unconditional logistic regression adjusting by age, sex, education, and occupational exposure to pesticides. RESULTS: Household insecticides did not increase risk of lymphoma (all subtypes), Hodgkin's lymphoma, B-cell lymphoma, and the major B-cell lymphoma subtypes. The risk of multiple myeloma (MM) but not the other subtypes showed a non-significant upward trend (p = 0.203) with increasing quartiles of days of use in the time window when propoxur was the most popular household insecticide. CONCLUSIONS: Our results suggest no association between the household use of insecticides and the risk of lymphoma. Further studies are warranted to confirm or discard an association between MM risk and the use of propoxur.

Epidemiology of Chronic Lymphocytic Leukemia in Sardinia, Italy (1974-2003).

Several reports have described a worldwide increasing incidence of chronic lymphocytic leukemia (CLL) dating back seven to eight decades. Although genetic susceptibility would be an implausible explanation, the determinants of this upward trend and its spatial coordinates are poorly understood. We explored CLL incidence in Sardinia, Italy, using a validated database including the 1700 CLL cases diagnosed during 1974-2003. We applied Bayesian methods to map the CLL probability by administrative unit and Poisson regression analysis to investigate socioeconomic and environmental determinants adjusting by possible confounders. The standardized (Standard European population) incidence rate for the Sardinian population over the study period was 5.1 per 100,000 (95% confidence interval [CI] 4.9-5.3), increased annually by 5.8% (95% CI 5.7-6.0) consistently by sex and age, and was more noticeable in urban areas. Five administrative units exceeded the 95% posterior probability of an elevated CLL incidence: these were rural areas spread over the regional territory, not suggestive of spatial clustering. The Poisson regression analysis showed that the risk was elevated in urban areas (RR = 1.11, 95% CI 1.05-1.17), among residents ≥ 30 km from the nearest hospital (RR = 1.09, 95% CI 1.06-1.12), and with the local prevalence of cork harvesting (RR = 1.62, 95% CI 1.12-2.34). Our results suggest that better access to health care facilities and improvements in diagnostic efficacy might have generated the observed upward trend in CLL incidence, along with contributing environmental factors.

Gender and Nightshift Work: A Cross Sectional Study on Sleep Quality and Daytime Somnolence.

A few studies suggested that female nightshift workers suffer more frequently from sleep deprivation and insomnia. We conducted a cross-sectional survey in two different occupational settings to address gender-related differences in nightshift work adaptation. We used the Epworth Sleepiness Scale and the Pittsburgh Sleep Quality Index questionnaires to quantify daytime sleepiness and sleep quality among 156 workers, 91 from a ceramic tile factory and 65 healthcare workers, including hospital doctors, nurses, and nurse assistants. Seventy-three percent of participants (40 women and 74 men) were engaged in nightshift work. We used logistic regression analysis to predict daytime sleepiness and poor sleep quality as a function of personal and lifestyle variables and nightshift work. The female gender showed a strong association with both daytime sleepiness and poor sleep quality. Results were also suggestive of an increase in the risk of daytime sleepiness associated with nightshift work and being married. Our results confirm that women are especially vulnerable to sleep disruption. Promoting adaptation to nightshift work requires special attention towards gender issues.

Next Generation Sequencing for miRNA Detection on the Exhaled Breath Condensate: A Pilot Study.

Introduction: Exhaled breath condensate (EBC) sampling has been suggested as a less-invasive and cost-effective method to detect biological macromolecules, including miRNA. To explore the feasibility of its use as a biomarker of early effects of asbestos exposure, we conducted a preliminary test on male volunteers by comparing the miRNA profile in the EBC and the plasma using 2 different sequencing platforms. Methods: Six male volunteers, all retired and unexposed to dust or fumes, participated in the test. RNA was extracted from 200 µL EBC samples and same-size plasma samples. Sample aliquots were processed in 2 laboratories using 2 different sequencing platforms: a MiSeq Illumina® platform and a more performing HiSeq Illumina® platform. Results: The HiSeq3000® sequencing platform identified twice as many unique molecular indexes (UMI)-validated miRNA as the MiSeq® platform. The Spearman's correlation coefficient between EBC counts and plasma counts was significant in 5/6 subjects with either platform (MiSeq® = 0.128-0.508, P = .026-<.001; HiSeq® = 0.156-0.412, P = .001-<.001). The intraclass correlation coefficient confirmed the consistency of the miRNA profile over the 6 participants with both biospecimens. Exploring the agreement between the EBC and plasma samples with Bland-Altman plots showed that using the HiSeq3000® platform substantially improved the EBC miRNA detection rate. Conclusion: Our preliminary study confirms that, when using the HiSeq® sequencing platform, EBC sampling is a suitable, non-invasive method to detect the miRNA profile in healthy subjects.

What role for asbestos in idiopathic pulmonary fibrosis? Findings from the IPF job exposures case-control study.

BACKGROUND: Asbestos has been hypothesised as the cause of the recent global increase in the incidence of 'idiopathic' pulmonary fibrosis (IPF). Establishing this has important diagnostic and therapeutic implications. The association between occupational asbestos exposure and IPF, and interaction with a common (minor allele frequency of 9% in European populations) genetic variant associated with IPF, MUC5B rs35705950, is unknown. METHODS: Multicentre, incident case-control study. Cases (n=494) were men diagnosed with IPF at 21 UK hospitals. Controls (n=466) were age-matched men who attended a hospital clinic in the same period. Asbestos exposure was assessed at interview using a validated job exposure matrix and a source-receptor model. The primary outcome was the association between asbestos exposure and IPF, estimated using logistic regression adjusted for age, smoking and centre. Interaction with MUC5B rs35705950 was investigated using a genetic dominant model. RESULTS: 327 (66%) cases and 293 (63%) controls ever had a high or medium asbestos exposure risk job; 8% of both cases and controls had cumulative exposure estimates ≥25 fibre ml⁻¹ years. Occupational asbestos exposure was not associated with IPF, adjusted OR 1.1 (95% CI 0.8 to 1.4; p=0.6) and there was no gene-environment interaction (p=0.3). Ever smoking was associated with IPF, OR 1.4 (95% CI 1 to 1.9; p=0.04) and interacted with occupational asbestos exposure, OR 1.9 (95% CI 1 to 3.6; p=0.04). In a further non-specified analysis, when stratifying for genotype there was significant interaction between smoking and work in an exposed job (p<0.01) for carriers of the minor allele of MUC5B rs35705950. CONCLUSION: Occupational asbestos exposure alone, or through interaction with MUC5B rs35705950 genotype, was not associated with IPF. Exposure to asbestos and smoking interact to increase IPF risk in carriers of a common genetic variant, the minor allele of MUC5B rs35705950. TRIAL REGISTRATION NUMBER: NCT03211507.

Byssinosis and lung health among cotton textile workers: baseline findings of the MultiTex trial in Karachi, Pakistan.

OBJECTIVES: To assess the association of exposure in cotton mills in Karachi with different definitions of byssinosis and lung health. METHODS: This cross-sectional survey took place between June 2019 and October 2020 among 2031 workers across 38 spinning and weaving mills in Karachi. Data collection involved questionnaire-based interviews, spirometry and measurements of personal exposure to inhalable dust. Byssinosis was defined using both WHO symptoms-based (work-related chest tightness), and Schilling's criteria (symptoms with decreased forced expiratory volume in 1 s (FEV1). Values of FEV1/forced vital capacity ratio below the lower limit of normality on postbronchodilator test were considered as 'chronic airflow obstruction' (CAO). RESULTS: 56% of participants had at least one respiratory symptom, while 43% had shortness of breath (grade 1). Prevalence of byssinosis according to WHO criteria was 3%, it was 4% according to Schilling's criteria, and likewise for CAO. We found low inhalable dust exposures (geometric mean: 610 µg/m3). Cigarette smoking (≥3.5 pack-years), increasing duration of employment in the textile industry and work in the spinning section were important factors found to be associated with several respiratory outcomes. CONCLUSION: We found a high prevalence of respiratory symptoms but a low prevalence of byssinosis. Most respiratory outcomes were associated with duration of employment in textile industry. We have discussed the challenges faced in using current, standard guidelines for identifying byssinosis.

Association of respiratory symptoms and lung function with occupation in the multinational Burden of Obstructive Lung Disease (BOLD) study.

BACKGROUND: Chronic obstructive pulmonary disease has been associated with exposures in the workplace. We aimed to assess the association of respiratory symptoms and lung function with occupation in the Burden of Obstructive Lung Disease study. METHODS: We analysed cross-sectional data from 28 823 adults (≥40 years) in 34 countries. We considered 11 occupations and grouped them by likelihood of exposure to organic dusts, inorganic dusts and fumes. The association of chronic cough, chronic phlegm, wheeze, dyspnoea, forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)/FVC with occupation was assessed, per study site, using multivariable regression. These estimates were then meta-analysed. Sensitivity analyses explored differences between sexes and gross national income. RESULTS: Overall, working in settings with potentially high exposure to dusts or fumes was associated with respiratory symptoms but not lung function differences. The most common occupation was farming. Compared to people not working in any of the 11 considered occupations, those who were farmers for ≥20 years were more likely to have chronic cough (OR 1.52, 95% CI 1.19-1.94), wheeze (OR 1.37, 95% CI 1.16-1.63) and dyspnoea (OR 1.83, 95% CI 1.53-2.20), but not lower FVC (ß=0.02 L, 95% CI -0.02-0.06 L) or lower FEV1/FVC (ß=0.04%, 95% CI -0.49-0.58%). Some findings differed by sex and gross national income. CONCLUSION: At a population level, the occupational exposures considered in this study do not appear to be major determinants of differences in lung function, although they are associated with more respiratory symptoms. Because not all work settings were included in this study, respiratory surveillance should still be encouraged among high-risk dusty and fume job workers, especially in low- and middle-income countries.

COVID-19 and non-Hodgkins lymphoma: a common susceptibility pattern?

ObjectivTo explore the link between COVID-19 incidence, socio-economic covariates, and NHL incidence. DesignEcological study design. SettingSardinia, Italy. ParticipantsWe used official reports on the total cases of COVID-19 in 2020, published data on NHL incidence, and socio-economic indicators by administrative unit, covering the whole regional population. Main outcomes and measuresWe used multivariable regression analysis to explore the association between the natural logarithm (ln) of the 2020 cumulative incidence of COVID-19 and the ln-transformed NHL incidence in 1974-2003, weighing by population size and adjusting by socioeconomic deprivation and other covariates. ResultsThe cumulative incidence of COVID-19 increased in relation to past incidence of NHL (p < 0.001), socioeconomic deprivation (p = 0.006), and proportion of elderly residents (p < 0.001) and decreased with urban residency (p = 0.001). Several sensitivity analyses confirmed the finding of an association between COVID-19 and NHL. ConclusionThis ecological study found an ecological association between NHL and COVID-19. If further investigation would confirm our findings, shared susceptibility factors should be investigated among the plausible underlying mechanisms. Strengths and limitations of this studyO_LIThis study exploited the availability of incidence data for non-Hodgkins lymphoma over a 30-year time frame and the 2020 cumulative incidence data for COVID-19 available for all administrative units in the Sardinia region, Italy. C_LIO_LIUsing an ecological study design, we observed that COVID-19 occurrence increased with past incidence of non-Hodgkins lymphoma. C_LIO_LILimitations of the ecological study design require further investigation for confirmation and for identification of susceptibility factors possibly shared between the two diseases. C_LI

COVID-19 incidence in a cohort of public transport workers.

BACKGROUND: Previous research has shown an excess risk of COVID-19 among several occupations, but data on public transport workers are scarce. To investigate the occupational risk posed by contact with the public, we followed up the incidence of COVID-19 in a cohort of public transport workers. METHODS: We identified the incident cases of COVID-19 between 1 September 2020 - 6 May 2021 in a cohort of 2,052 employees of a public transport agency in Sardinia, Italy. The diagnosis of COVID-19 was based on a positive molecular test. To calculate the expected events, we applied the age- and gender-specific incidence rates of the regional population in the same time period to the correspondent strata of the study cohort. We estimated the relative risk (RR) of COVID-19 as the ratio between the observed and the expected events and its 95% confidence interval (95% C.I.) among the total cohort and in two sub-cohorts: bus drivers, and the rest of the personnel (administrative staff, train and metro drivers, workers in the mechanical shop, and in the railroad maintenance, and security). RESULTS: Bus drivers run an elevated risk of COVID-19 (RR = 1.4, 95% C.I. 1.07 - 1.79). There was no excess risk among the sub-cohort including the rest of the personnel. CONCLUSIONS: Our study suggests an excess risk of COVID-19 among bus drivers even in a relatively low incidence area, which could imply inadequacy of the preventive measures in place. Further, larger size studies with detailed information on personal and lifestyle characteristics are warranted.