ABSTRACT
SARS-CoV-2 viral load is associated with disease severity. A better understanding of immunological mechanisms involved in viral clearance is crucial to guide new therapeutic strategies. Here, we studied the timing of viral clearance in relation to 122 immune parameters in 150 hospitalized COVID-19 patients. Delayed viral clearance was associated with more severe disease, which occurred after the virus had been cleared in most cases. Paradoxically, delayed viral clearance was associated with over time higher maximum levels of SARS-CoV-2 specific IgG, IgA, and neutralizing antibodies, increased numbers of eosinophils, monocytes, and pro-inflammatory cyto-/chemokines. In contrast, early viral clearance and less critical illness correlated with higher levels of CD4 + and CD8 + T cells. Collectively, our data show that absence of rapid T cell control corresponds with delayed clearance and aberrant antibody and cytokine profiles. Viral clearance often precedes critical illness, which suggests immunopathology as underlying mechanism. These data can guide treatment strategies.