Abstract
The COVID-19 pandemic continues to highlight the significant impact of pre-existing comorbidities on disease progression and patient outcomes due to the risk factors for severe disease in unvaccinated patients. We evaluated the association between several clinical/laboratory findings and comorbidities in a cohort of unvaccinated patients hospitalized in the intensive care unit in Recife, Pernambuco State, Brazil. We enrolled 36 unvaccinated volunteers, and performed clinical, biochemical, hematological, and microbiological analyses. Cellular immunity, cytokine measurement, and gene expression were also analyzed. Additionally, serum samples were submitted to serological and neutralization assays by using SARS-CoV-2 B.1 Lineage, Gamma (P.1), Delta (B.1.617.2-like), and Omicron (BA.1) variants. Hypertension was the most common comorbidity in patients requiring oxygen supplementation, followed by diabetes and metabolic syndrome. Such conditions were linked to increased disease severity, with elevated levels of inflammatory biomarkers (D-dimer, C-reactive protein), neutrophilia, and lymphopenia. Chronic inflammation, which is often seen in diabetes and metabolic syndrome, worsens the inflammatory response triggered by COVID-19, which exacerbates endothelial injury and leads to a hypercoagulable state. Additionally, patients with comorbidities had impaired humoral immunity, and showed reduced seroconversion and neutralizing activity, which hindered their ability to combat the virus effectively. Furthermore, this study revealed that patients with diabetes and metabolic syndrome had an exaggerated Th17-driven immune response, which contributed to severe outcomes and multi-organ failure. These findings underscore the importance of personalized care and targeted interventions for patients with comorbidities, thus highlighting the need for further research on metabolic disorders, immune dysfunction, and COVID-19.