The EPICOVID19-BS epidemiological survey is a continuation of the EPICOVID-19 study, which targeted individuals aged 18 years and older residing in Italy and was led by the same working group. EPICOVID19 included a phase I epidemiological survey to determine the prevalence of suspected SARS-CoV-2 infection and associated factors in a sample of 201,121 adults residing in Italy during the first wave of the pandemic (April–May 2020) [23]. In addition, a phase II follow-up study of 43,473 individuals was conducted in Italy in January–February 2021 [24].

In the present study, performed from September 2021 to February 2022, the rate of positive COVID-19 cases was 20.4%, which is higher than the rate of 13.2% found in the follow-up EPICOVID19 study performed in the general population, as expected [23]. Few studies have reported the prevalence of positive NPS/COVID-19 in the BS population. In a retrospective observational cohort study of 236 Iranian patient with severe obesity following (surgical group) or candidates (nonsurgical group) for BS contacted by questionnaire between November 2020 and March 2021, the incidence of probable COVID-19 was reported to be 20.6% in the surgical group and 26.08% in the non-surgical groups [19]. In the study by Romero-Velez and colleagues, 190 patients with severe obesity are at high risk of severe disease secondary to COVID-19 were contacted by telephone from January 2020 to March 2020, and those who underwent bariatric surgery during the development of the pandemic reported COVID-19 compatible symptoms 30 days after surgery at a rate of 10.7% and 3.4% went on to test positive [20]. In Italy, Marchesi et al. conducted a study of 594 patients from various Italian bariatric centres who underwent a telephone survey from April to August 2020; the authors reported that the rate of probable cases was 14.4% in the operated group and 23.7% in the candidate group [16]. Marinari et al. performed a structured interview in January–February 2020 with 840 patients who had undergone surgery before the outbreak and found only 5 cases of infection (0.6%) without mortality [21].

Regarding the sociodemographic characteristics of the sample, we enrolled more females than males with an average age in the 40–49 age group, and a majority of participants with a medium level of education. This sex disparity may be partly due to the fact that females are more likely than males to undergo weight loss surgery, with recent global reports suggesting that 70% of patients undergoing bariatric surgery are females [27]. No statistically significant differences between sex, age and educational level in the occurrence of COVID-19 were observed.

Instead, we found a significant difference in terms of occupational risk categories, with 29 (39%) of 74 patients working in the healthcare sector contracting SARS-CoV-2. This is consistent with the scientific literature on occupational risk factors: according to a meta-analysis of 97 studies by Gholami and colleagues, healthcare workers reported the highest rate of infection [28].

The authors of the phase I EPICOVID19 study took into account the number of comorbidities without separating the reported chronic diseases. As these subjects were patients undergoing BS, it is consistent that the types and frequencies of pathologies in EPICOVID19-BS differ from those in the study by Adorni F. et al. (2020): the most common chronic diseases were hypertension (23.8% of the enrolled subjects), depression and/or anxiety (8.7% of the subjects), dyslipidaemia (4.8% of the subjects), diabetes (3.9% of the subjects) and diseases of the immune system (8.1% of the total subjects, of which 12.5% of the total positive cases. Obesity is known to reduce self-tolerance mechanisms by promoting a pro-inflammatory environment for the development of autoimmune diseases, such as Hashimoto's thyroiditis; the aetiological agent of COVID-19, likewise, may also generate a cytokine storm, and in some cases may even be a disease trigger or precipitating factor. However, the relationship between autoimmune disease and susceptibility to SARS-CoV-2 is unclear [29]. When information on adverse environmental, food or pharmacological allergic reactions and previous infections were taken into account, previous cytomegalovirus infection appeared to increase the probability of contracting SARS-CoV-2. This observation is supported by the results of a retrospective study investigating the CMV serostatus of non-geriatric patients admitted to the ICU for COVID-19, which found that the CMV seropositivity, in contrast to herpes simplex virus seropositivity used as a control, could be a strong marker for detecting a higher risk of COVID-19 in younger subjects in the absence of other diagnosed comorbidities [30].

The use of medication was almost universal, but the following stood out: anti-inflammatory drugs, taken as needed, mainly to relieve joint pain and chronic low back pain, followed by anti-hypertensive drugs to control the main cardiovascular complication of obesity; more than half of the sample, suffering from vitamin D insufficiency or deficiency, typical of obesity, reported taking specific supplements instead, while 57.3% of them took multivitamins to correct multiple deficiencies. We found that of the 129 subjects who reported taking anti-inflammatory drugs, about 24% contracted SARS-CoV-2 infection. Several pharmacoepidemiologic studies confirm that exposure to non-steroidal anti-inflammatory drugs in viral or bacterial lung infections may increase the risk of severe complications, such as pleural empyema, necrotising pneumonia, or lung abscess [31].

Total cholesterol at or above the upper limit of normal, but without a diagnosis of dyslipidaemia, appeared to be lower in positive COVID-19 cases, as was the presence of metabolic syndrome. Indeed, we also found that of 194 patients diagnosed with metabolic syndrome as defined by the NCEP guidelines (ATP III) [32], 84% did not have COVID-19, which is not reflected in the literature where, for example, in a sample of 8885 subjects, the cumulative incidence of COVID-19 was found to be higher in patients with metabolic syndrome [33]. Lipidomic studies have shown that lipids are essential for viruses to cross host cell membranes and that enveloped coronaviruses in particular can alter intracellular metabolism and signaling to facilitate their replication. SARS-CoV-2 targets lipid droplets and exploits endosomes to make copies of itself; this causes the endoplasmic reticulum to produce misfolded proteins that trigger a chain reaction leading to downstream stimulation of sterol regulatory-element binding protein-1 (SREBP-1), which transcribes lipid down-regulation genes. The result is the most common lipid profile alterations reported in the literature, namely a decrease in total cholesterol, Apolipoprotein A1 levels, and a concomitant increase in circulating TG levels. Furthermore, the hyperinflammatory state affects several lipid biosynthetic pathways, and the more HDL-C and its major apolipoprotein are reduced, the greater the severity of disease, mortality and levels of inflammatory markers [34]. In addition to the lipid picture, it is evident that the sample reference population is also partially affected by pre-diabetes or overt diabetes, a condition that has not been shown to be negatively or positively associated with COVID-19 incidence and prognosis, although studies have reported that both glycaemia and glycated haemoglobin are significantly higher in affected individuals [35].

Compared to the study by Adorni F. et al. (2020) [23], where the asymptomatic rate was 7.7%, we found an asymptomatic rate of 18.4% in our study. Most subjects experienced flu-like symptoms, such as headache, myalgia, sore throat/rhinorrhoea and fever in addition to loss of smell and taste, a pathognomonic feature of earlier waves of SARS-CoV-2 infection and suggested as key symptoms of mild-to-moderate COVID-19 patients [36].

As evidence of the insidious mode of transmission of the virus through the air or by close direct contact with droplets, as highlighted in the scientific literature, a much higher frequency of subjects who fell ill reported having had "close contact" with confirmed COVID-19 cases, one third of the COVID-19 positive group at least once without wearing a mask to protect the oronasal mucosa. However, the open awareness of the high level of contagiousness, which also exploited a conspicuous proportion of asymptomatic subjects as unwitting carriers of the disease, was not sufficient to induce subjects without suspicious symptoms to perform a precautionary nasopharyngeal swab, which later proved negative, after contact with confirmed COVID-19 cases. The strong ego-syntonic psychopathological correlate supporting and maintaining their state of obesity was manifested in an overestimation of their health status, which ended in their low perception of anxiety and stress due to the new pandemic challenge they had to face. It is now well established that each BMI point above the range defined as "normal weight" increases the rate of hospitalisation, use of intensive care, illness and length of convalescence: however, our study showed a low percentage of hospitalisations among the COVID-19 positive (9.6%), of whom five subjects required oxygen therapy and one of them was admitted to the sub-intensive care unit and received non-invasive ventilation, and none were intubated. For example, Lighter et al. reported 29% and 22% of acute admissions due to COVID-19 and 23% and 33% of ICU admissions in US patients aged < 60 years with a BMI between 30 and 34 and greater than 35, respectively [6]. Our findings were consistent with the results from two recent meta-analyses involving 150,848 [17] and 151,475 [18] patients, respectively, which showed that BS is associated with a reduced severity of COVID-19 infection, as evidenced by a reduced risk of mortality, hospital and ICU admission, mechanical ventilation, and shorter hospital stay in the surgical group of patients with obesity after SARS-CoV-2 infection compared with the non-operative group.

The contribution of obesity to the severity of COVID-19 can be explained in several ways [4]. Adipose tissue has higher levels of ACE2 angiotensin-converting enzyme 2 (ACE2) receptors, the key entry mechanism of SARS-CoV-2, than human lung, a major target tissue affected by viral infection. In patients with obesity, adipose tissue grows by hyperplasia, resulting in an increased number of cells expressing ACE2, increasing the likelihood of SARS-CoV-2 entry [37]. Obesity also affects respiratory function through several mechanisms, including mechanical changes due to fat deposition on the chest wall, diaphragm, and upper airways, which can lead to restrictive lung damage [38]. In addition, individuals with obesity experience persistent chronic low-grade systemic inflammation and disproportionate adipocyte volume resulting in low blood perfusion. Adipose tissue hypoxia increases pro-inflammatory signals, which in turn cause dysregulation of the immune response. COVID-19 cases with obesity are more likely to develop critical symptoms due to the well-known 'cytokine storm' [39]. Weight loss and long-term reduction in adipose tissue as a result of BS might help to reduce the number of ACE2-expressing cells, improve respiratory function [40] and reduce inflammatory markers such as C-reactive protein (CRP) and IL-6 [41].

Regarding lifestyle (smoking, alcohol, dietary habits), questionnaire responses showed no significant differences between positive and negative COVID-19 cases. Overall, most enrolled subjects reported light to moderate alcohol consumption and only ¼ were current smokers. Given the enforced confinement to the home during the first wave of the pandemic, there was no change in physical activity, sedentary behaviour, sleep duration or eating behaviours typical of individuals with severe obesity, such as snacking, skipping meals and eating sweet, fried or fast food. We must therefore give the benefit of the doubt and assume that the patient with obesity who presents to a bariatric surgery unit either has a misconception about his disease and his bad habits, or is well aware of them but is reluctant and ashamed to admit his dysfunctional behaviour. Since the beginning of the pandemic, there has been a significant difference in the frequency of visits to national health facilities for non-severe health problems between COVID-19 infected and negative patients. In the present study, we observed that in the former, it was only 9.9% compared with 22.4% of those who did not become ill; conversely, in the latter, it was 20.4% of those who became ill compared with 15.9% of those who did not, apparently because of the presence of typical symptoms or a strong suspicion of positivity; the latter either because of previous close contact with other COVID-19-positive individuals or because at least one of them had a positive molecular swab result. During the study period, hospitals were facing a crisis of limited human resources, with entire wards, operating theatres and outpatient clinics being reserved for COVID-19 emergencies. This, combined with the fear of infection, led to a reduction in general practitioner visits, outpatient visits, intensive care, pathology and oncology screening, with the result that the frailest population, including the overweight and obese, ended up with a chronic disease that was not previously present.

There are several limitations that need to be considered. Due to the cross-sectional and observational design, it is not possible to draw causal inferences. In addition, the study is voluntary, which may affect the generalisability of the results. In fact, some of the characteristics of the sample may not be representative of the Italian adult population undergoing BS, thus comparison with other cohorts should be made with caution. Another limitation of our study is the use of patient self-report data, which may have introduced measurement error and recall bias. This may have led to misclassification of participants' COVID-19 status or exposures. However, it is reasonable to assume that non-differential misclassification may have occurred, where the likelihood of misclassification of exposure is independent of disease status and vice-versa, increasing the similarity between the exposed and unexposed groups. A future well-designed longitudinal prospective cohort study or randomised controlled clinical trial, including radiographs and chest CT scans at hospital admission and discharge, and postoperative follow-up of enrolled patients, is needed to more accurately assess exposure and clinical risk in this vulnerable population subgroup. Nevertheless, the study has notable strengths. First, the study included a large sample of patients undergoing bariatric surgery in Italy. Second, although the data were self-reported, the entire sample underwent an NPS or ST, providing a snapshot of the positivity rate in this specific population for which data are scarce. Third, the sample was well characterised by the extensive collection of socio-demographic, behavioural and psychological data through the web survey, combined with the previously collected detailed clinical information and laboratory parameters. Fourthly, the use of a web-based survey to collect data can overcome the higher costs associated with active follow-up or interviewer bias typical of telephone survey, as it is inexpensive and can rapidly involve a large number of people regardless of geographical distance.