Performance of serum apolipoprotein-A1 as a sentinel of Covid-19

Abstract

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, 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 serum apolipoprotein-A1 during the first 34 weeks of 2020 in a population that is routinely followed for a risk of liver fibrosis risk in the USA (212,297 serum) and in France (20,652 serum) in relation to a local increase in confirmed cases, and in comparison to the same period in 2019 (266,976 and 28,452 serum, respectively). 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 serum apolipoprotein-A1 levels in the survey populations began decreasing in January 2020, compared to the same period in 2019. This decrease was highly correlated with the daily increase in confirmed Covid-19 cases in the following 34 weeks, both in France and USA, including the June and mid-July recovery periods in France. Apolipoprotein-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. The adjusted risk ratio of apolipoprotein-A1 for survival without transfer to intensive care unit was 5.61 (95%CI 1.02-31.0; P = 0.04).

Conclusion: Apolipoprotein-A1 could be a sentinel of the pandemic in existing routine surveillance of the general population. NCT01927133, CER-2020-14.

Conflict of interest statement

TP has several USPTO patents related to the performance of Apoa1 in patients with liver disease, including #10,198,552 Method of diagnosis of fibrotic diseases, #7,860,656 Diagnosis method of hepatic steatosis using biochemical markers, 7,856,319, Diagnosis method of alcoholic steato-hepatitis using biochemical markers, #7,225,080 Diagnosis method of inflammatory, fibrotic or cancerous disease using biochemical markers, and # 6,631,330 Diagnosis method of inflammatory, fibrotic or cancerous disease using biochemical markers, and applications pending: #20200011879 Method of diagnosis of drug induced liver injury, 20190265241 Method of diagnosis of non-alcoholic fatty liver diseases, #3 20140329260 Method of diagnosis of fibrotic diseases, and #20090111132 Diagnosis method of hepatic steatosis using biochemical markers. The data underlying the findings described in the manuscript are fully detailed including the confounding factors, without restriction, in the numerous supplementary files. The commercial affiliation does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Quantitative decrease of apolipoprotein-A1 by cohort.

Apolipoprotein-A1 decreased (P

Fig 2. Proportion of serum with low apolipoprotein-A1 by cohorts.

Low apolipoprotein-A1 was defined as below 1.25 g/L. Details in Table 2.

Fig 3. Decrease of apolipoprotein-A1 by gender and age in US cohort.

The same significant kinetics were observed, P

Fig 4. Absence of haptoglobin increase in the first 34 weeks of 2020 in the US cohort.

Only the French cohorts at high risk of Covid-19 patients had a significant increase in haptoglobin.

Fig 5. Number of confirmed Covid-19 cases per day and proportion of low (

The red graph is the number of confirmed cases per day in logarithmic scale. The black line is the daily mean proportion of low apolipoprotein-A1 (

Fig 6. Apolipoprotein A1 median with IQR between the 6 populations.

CPAM: general population assessing specificity of apolipoprotein-A1 in the sentinel context of use. Three populations were used for assessing higher risk of false positive: severe acute alcoholic hepatitis (ASH), drug induced liver disease (DILI), and rheumatologic disease (RHE). The blood donors population (BD) was at lower risk of false positive.

Fig 7. Haptoglobin median with IQR between the 6 populations.

Fig 8. Area under the ROC curves (AUROC) of each FibroTest components.

Fig 9. Survival without transfer to intensive care unit (ICU).

The 71 patients with apolipoprotein-A1 value > = 0.84 g/L, the median value at inclusion, had a significant higher survival without ICU (93.0%;87.0–98.9) than the 65 patients with lower value (75.8%;65.1–86.5; P = 0.02).

Fig 10. Serum apolipoprotein-A1 prospective 256 repeated measurements in 104 patients with Covid-19, who survived without transfer to intensive care unit.

The median range interval between the first and the last serum was 11 days (IQR 8–16). Significant differences between ranks P

Fig 11. Serum apolipoprotein-A1 prospective 30 repeated measurements in 16 patients with Covid-19, who were transferred to intensive care unit and survived.

The median interval between the four serum was 11 days (IQR 8–16). Significant differences between ranks P

Fig 12. Serum haptoglobin prospective 256 repeated measurements in 104 patients with Covid-19, who survived without transfer to intensive care unit.

The median range interval between the first and the last serum was 11 days (IQR 8–16). Significant difference between ranks P

Fig 13. Serum haptoglobin 30 repeated measurements in 16 patients with Covid-19, who survived among those transferred to intensive care unit.

The median range interval between the first and the last serum was 11 days (IQR 8–16). Significant differences between ranks P