Serological markers and Post COVID-19 Condition (PCC) – A rapid review of the evidence

Background Post COVID-19 Condition (PCC) is highly heterogeneous, often debilitating, and may last for years after infection. The etiology of PCC remains uncertain. Examination of potential serological markers of PCC, accounting for clinical covariates, may yield emergent pathophysiological insights. Methods In adherence to PRISMA guidelines, we carried out a rapid review of the literature. We searched Medline and Embase for primary observational studies that compared IgG response in individuals who experienced COVID-19 symptoms persisting ≥12 weeks post-infection with those who did not. We examined relationships between serological markers and PCC status and investigated sources of inter-study variability, such as severity of acute illness, PCC symptoms assessed, and target antigen(s). Results Of 8,018 unique records, we identified 29 as being eligible for inclusion in synthesis. Definitions of PCC varied. In studies that reported anti-nucleocapsid (N) IgG (n=10 studies; n=989 participants in aggregate), full or partial anti-Spike IgG (i.e., the whole trimer, S1 or S2 subgroups, or receptor binding domain, n=19 studies; n=2606 participants), or neutralizing response (n=7 studies; n=1123 participants), we did not find strong evidence to support any difference in serological markers between groups with and without persisting symptoms. However, most studies did not account for severity or level of care required during acute illness, and other potential confounders. Conclusions Pooling of studies would enable more robust exploration of clinical and serological predictors among diverse populations. However, substantial inter-study variations hamper comparability. Standardized reporting practices would improve the quality, consistency, and comprehension of study findings.