Exploring the relationship between anellovirus load and clinical variables in hospitalized COVID-19 patients: Implications for immune activation and inflammation

Objectives: Anelloviruses have been linked with host-immunocompetence and inflammation. Here, we studied the anellovirus load in hospitalized COVID-19 patients.Methods: We collected samples of patients recruited in the DAWN-Plasma trial that received convalescent plasma (CP) therapy (four plasma units) combined with standard of care (SOC) or SOC of alone. Plasma samples were collected on day 0 and 6 of hospitalization and we quantified anellovirus load. With multivariate models, clinical variables were associated with changes in anellovirus load.Results: Samples were collected on day 0 and 6 of 150 patients (103 CP + SOC and 47 SOC). Anellovirus load was higher on day 0 compared to day 6 and we found a significant drop in SOC patients. Patients receiving immunosuppressive drug had a lower anellovirus load (coefficient: 1.021, 95% confidence interval [CI] 0.2701.772, P = 0.008), while patients admitted to the emergency room displayed a higher abundance on day 0 (1.308, 95% CI 0.443-2.173, P = 0.003). Unspecific markers of inflammation and organ damage, D-dimer (0.001, 95% CI < 0.001-0.001, P = 0.001) and lactate dehydrogenase (0.002, 95% CI 0.001-0.004, P = 0.044), were positively associated with anellovirus load. Finally, anellovirus load on day 0 (-39.9, 95% CI -75.72 to -4.27, P = 0.029) was negatively associated with SARS-CoV-2 antibody response on day.Conclusion: The results showed associations between clinical variables and anellovirus load in COVID-19 patients. Many variables share properties related to host immunocompetence or inflammation. Therefore, we expect that anellovirus abundance displays the net state of immune activation.