Multiple factors, from socioeconomic development to genetic background, can affect the regional impact of some diseases, and this has also been seen during the COVID-19 pandemic. The objective of this retrospective study was to characterize a population in the interior of Portugal regarding health status and COVID-19 epidemiology. Between October 2021 and January 2023, 1553 subjects residing in Beira Baixa, Portugal, were included. Using a self-report approach, demographic and clinical data were obtained. Blood group, blood pressure, peripheral oxygen saturation and anti-spike protein immunoglobulin concentration were also analyzed. Statistical analysis was performed using IBM SPSS Statistics. The average age of the participants was 48.95 (±14.43) years, with 64% being male and 36% being female. The most prevalent comorbidities were hypertension (19.2%), dyslipidemia (12.6%) and diabetes mellitus (6.6%). Half of the population was overweight, and more than half of the subjects had no history of tobacco consumption. Among the participants, 33% were infected with SARS-CoV-2: 70.1% had mild disease, 14.1% moderate disease and 1.4% severe disease. There was a very significant adherence to vaccination (97%). Previously infected or vaccinated people had higher anti-spike protein immunoglobulin values; this value depended on the vaccine administered (p < 0.001). Patients with autoimmune diseases and smokers had lower levels of anti-S IgG antibodies (p = 0.030 and p = 0.024, respectively). The severity of COVID-19 did not affect the concentration of anti-S IgG (p = 0.430). This study highlights the general health statuses and the impact of COVID-19 on a population in the Portuguese interior. Knowledge of the circulation and impact of the virus in this specific population can alert and assist in better interventions being conducted by health authorities.
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