Introduction:
The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to pose a global health crisis in spite of ongoing interventions such as vaccination (1, 2). Pathology of COVID-19 displays varied clinical manifestations ranging from no symptoms to critical systemic disease (3–5). Hypoxemia is a key signature that discriminates between mild and moderate to severe disease(6, 7). The role of lymphopenia as a defining cellular immune correlate of moderate to severe disease has been well established (8). However, underlying immune homeostatic mechanisms that might contribute to this phenotype remain largely unexplored (9, 10). Understanding and identifying such relationships, in context of vaccination history, would help to guide therapeutic efforts and to ensure optimal disease management of COVID-19. In this study we evaluated the contribution of key inflammatory, cellular homeostatic and mucosal migratory markers in distinct stages of COVID-19 pathogenesis. Our results highlight associations of IL-6, IL-15 and sMAdCAM with lymphopenia together with a heretofore undescribed role for detectable plasma IL-15 as marker associated with symptomatic progression.