Performance of serum apolipoprotein-a1 as a sentinel of COVID-19
Authors: T. Poynard, O. Deckmyn, M. Rudler, V. Peta, Y. Ngo, M. Vautier, S. Akhavan, V. Calvez, C. Franc, J. M. Castille, F. Drane, M. Sakka, D. Bonnefond-Rousselot, J. Marc Lacorte, D. Saadoun, Y. Allenbach, O. Benveniste, F. Gandjbakhch, J. Mayaux, O. Lucidarme, B. Fautrel, V. Ratziu, C. Housset, D. Thabut, P. Cacoub
Journal: Hepatology (2020)

Background: Since 1920, a decrease in serum cholesterol has been identified as a marker of severe pneumonia  We have assessed the performance of serum apolipoprotein-A1 (A1), the main transporter of HDL-cholesterol, to identify the early spread of coronavirus disease 2019 (Covid-19) in the general population and its diagnostic performance for the Covid-19 Methods: We compared the daily mean A1 during the first 26 weeks of 2020 in a population that is routinely followed for a risk of liver fibrosis risk in France (18,239 sera) and in the USA (161,655 sera) in relation to a local increase in confirmed cases, and in comparison to the same period in 2019 (respectively 26,513 and 211,419 sera) Linear regression curves with 95% confidence intervals between the mean daily serum levels of A1 were compared by the F-test, and a significant difference was defined as P <0 001  We prospectively assessed the sensitivity of this marker in an observational study of 136 consecutive hospitalized cases and retrospectively evaluated its specificity in 7,481 controls representing the general population Results: The mean A1 levels in these populations began decreasing in January 2020, compared to the same 26 weeks in 2019 This decrease was highly correlated to and in parallel with the daily increase in confirmed Covid-19 cases in the following 26 weeks, in both France (national and hospital cohort APHP-PSL) and USA, including the June recovery period in France Figure 1 shows the proportion of low A1 (<1 24 g/L) during the 26 weeks Same differences were observed after stratifications on the following confounding factors: previous years 2017-2018, age, gender, hepatitis C or non-alcoholic fatty liver disease, BMI, fasting glucose and triglycerides No similar changes were observed for ALT, AST, GGT, and haptoglobin A1 at the 1 25 g/L cutoff had a sensitivity of 90 6% (95%CI84 2-95 1) and a specificity of 96 1% (95 7-96 6%) for the diagnosis of Covid-19 The area under the characteristics curve was 0 978 (0 957-0 988), and outperformed haptoglobin and liver function tests For a prevalence of 1 8% (136/7617;95%CI 1 5-2 1) of Covid-19 cases, the positive predictive value (PPV) was 30 0% (95%CI 25 6-34 7) and the negative predictive value (NPV) was 99 8% (95%CI 99 7-99 9) When adjusted on the range of Covid-19 prevalence predicted in the French population, the PPV was 40 5% and NPV was 99 7% for the 2 8% lower limit, and PPV was 56 0% and NPV was 99 3% for the 7 2% higher limit In the prospective recovery subset repeated measurements showed an increase of A1 from 0 89 to 1 04 g/L in a median of 11 days (n=305;ANOVA P<0 01) Conclusion: Apolipoprotein-A1 could be both a sentinel of the pandemic in existing routine surveillance of the general population, as well as a candidate predictor of suspected Covid-19 in multivariate analysis in cases with a negative virological test