ABSTRACT
Background: A1 and HP serum levels are associated with, spread, severity and recovery of SI.1 Low A1 level measured 10 years prior to SI exposure, is also a clinical risk factor (fragility) for SI.2 In patients (Pts) it is difficult to assess the real number of days post infection (Dpi). The aim of this pilot study was to compare the A1 and HP dynamic changes during the first 4 weeks after SI in a nonhuman primate model, the macaque (NHP), that recapitulates mild COVID- 19 symptoms, in 2 ancillary experimental SI,3 vs Pts of an updated prospective observational study.1 Methods: NHP had 3-5 years of age, 2 female rhesus and 2 cynomolgus, and originating from Mauritian and Chinese AAALAC certified breeding centers, respectively, infected intranasally and intratracheally with 2×107 plaque-forming units of the clinical isolate hCoV-19/France/lDF0372/2020. Viral loads in nasopharyngeal, tracheal and rectal fluids were analyzed using an RT-qPCR assay, (Roche). Pts were those included in the observational study of SI in the GHPS hospital (intermediate severity 3to5 WHO grades), the Dpi being defined since the first symptom. A1 and HP were measured in all 283 Pts and in a subset of 58 with at least 3 repeated samples, a population (n=7482) representative of French population was used as Controls. Results: (Figure): In NHP, A1 had no significant changes from Dpi7 to Dpi26 (Panel A), contrarily to Pts who had lower values than Controls (blue box) (Repeated ANOVA Dunnets test) P<.001) before, during SI, and after recovery in all or repeated samples (Panel B). In NHP, HP was peaking at 7Dpi, close to the peak of nasal viral loads, still elevated at 20Dpi (Panel C);CRP in the same HP was peaking later at 13Dpi, and still high at 20Dpi.3 In Pts, HP changes were similar with a peak at 14Dpi and returned to normal values at 60Dpi (Panel D). Conclusion: These results validate in NHP the HP changes observed in hospitalized patients with intermediate severity SI. HP is an earlier marker of SI than CRP, and ApoA1 changes should be evaluated in NHP with shorter Dpi.
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 (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.