Comparison of serum apolipoprotein-a1 (a1) and haptoglobin (hp) kinetics during sars-cov2 infection (si) in macaques and humans

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.