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Summary: Biomarkers for monitoring COVID-19 disease course are lacking. Study aim was to identify biomarkers associated with disease severity, survival, long-term outcome, and Long COVID. As excessive macrophages activation is a hallmark of COVID-19 and complement activation is key in this, we selected the following proteins involved in these processes: PTX3, C1q, C1-INH, C1s/C1-INH, and sMR. EDTA-plasma concentrations were measured in 215 patients and 47 controls using ELISA. PTX3, sMR, C1-INH, and C1s/C1-INH levels were associated with disease severity. PTX3 and sMR were also associated with survival and long-term immune recovery. Lastly, sMR levels associate with ICU admittance. sMR (AUC 0.85) and PTX3 (AUC 0.78) are good markers for disease severity, especially when used in combination (AUC 0.88). No association between biomarker levels and Long COVID was observed. sMR has not previously been associated with COVID-19 disease severity, ICU admittance or survival and may serve as marker for disease course.