Autoantibodies against apolipoprotein A-1 after COVID-19 predict symptoms persistence

Background SARS-CoV-2 infection triggers different auto-antibodies, including anti-apolipoprotein A-1 IgGs (AAA1), which could be of concern as mediators of persistent symptoms. We determined the kinetics of AAA1 response over after COVID-19 and the impact of AAA1 on the inflammatory response and symptoms persistence. Methods All serologies were assessed at one, three, six and twelve months in 193 hospital employees with COVID-19. ROC curve analyses and logistic regression models (LRM) were used to determine the prognostic accuracy of AAA1 and their association with patient-reported COVID-19 symptoms persistence at 12 months. Interferon (IFN)-alpha and-gamma production by AAA1-stimulated human monocyte-derived macrophages (HMDM) was assessed in vitro. Results AAA1 seropositivity was 93% at one month and declined to 15% at 12 months after COVID-19. Persistent symptoms at 12 months were observed in 45.1% of participants, with a predominance of neurological (28.5%), followed by general (15%) and respiratory symptoms (9.3%). Over time, strength of correlations between AAA1 and anti-SARS-COV2 serologies decreased, but remained significant. From the 3(rd) month on, AAA1 levels predicted persistent respiratory symptoms (area under the curves 0.72-0.74; p < 0.001), independently of disease severity, age and gender (adjusted odds ratios 4.81-4.94; p = 0.02), while anti-SARS-CoV-2 serologies did not. AAA1 increased IFN-alpha production by HMDMs (p = 0.03), without affecting the IFN-gamma response. Conclusion COVID-19 induces a marked though transient AAA1 response, independently predicting one-year persistence of respiratory symptoms. By increasing IFN-alpha response, AAA1 may contribute to persistent symptoms. If and how AAA1 levels assessment could be of use for COVID-19 risk stratification remains to be determined.