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.