The Clinical Presentations of Patients With COVID-19 in the Omicron Era: Missed Opportunities in the Antiviral Treatment of SARS-CoV-2 Infections

COVID-19 has posed a significant global health challenge. SARS-CoV-2 has accumulated several mutations and adapted to humans, with its clinical manifestations evolving from severe bilateral interstitial pneumonia with respiratory failure to predominantly milder forms of disease. Effective antiviral treatments have been developed but remain underutilized, even in high-risk individuals. We conducted a retrospective study on patients hospitalized for COVID-19 in our hospital's Infectious Disease/COVID-19 wards. Written informed consent was obtained from all participants. Demographic, clinical, and therapeutic data were collected. Due to limited viral sequencing, time periods were categorized based on the dominant epidemiological variants: Wild-Type/Alpha (February 2020 to June 2021), Delta (July to December 2021), and Omicron (January 2022 to January 2024). We included 606 patients, of whom 381 (62.9%) were male, with a mean age of 65.5 years (±17.0) and a mean BMI of 26.4 kg/m² (±5.7). The most common comorbidities were arterial hypertension (43.8%), cardiovascular diseases (25.2%) and diabetes (21%). A total of 380 (62.7%)of patients were infected with the Wild-Type variant, 49 (8.1%) with Wild-Type/Alpha, 17 (2.8%)with Alpha, 20 (3.3%)with Alpha/Delta,45 (7.4%)with Delta, 4 (0.7%)with Delta/Omicron, and 91 (15%) with Omicron. The clinical presentation evolved significantly: we observed a decline in the prevalence of fever (78% in Wild-Type vs. 57% in Omicron), myalgia (19% vs. 4%), diarrhoea (15% vs. 3%), rhinorrhoea (9% vs. 1%), and ageusia, which disappeared entirely in Omicron cases. In contrast, neurological symptoms became more frequent, increasing from 13% in Wild-Type to 27% in Omicron infections, with delirium being the most common manifestation (59% of neurological cases). In-hospital mortality was significantly lower with Omicron variants (5.5%) as compared to the older ones (Delta 15.9%, WT/alpha 13.2%, p < 0.001). Out of 256 participants with risk factors for severe disease, 116 (45.3%) could have potentially been treated with anti-SARS-CoV-2 drugs for early treatment: only two patients (1.7%) were treated with such drugs in out-of-hospital settings. These results underscore the importance of targeted vaccination campaigns, enhanced access to early antiviral therapies, and further research to understand evolving clinical patterns and optimize therapeutic strategies.