Clinical and serological predictors of post covid-19 condition – findings from a canadian prospective cohort study

Introduction More than three years into the pandemic, there is persisting uncertainty as to the etiology, biomarkers, and risk factors of Post COVID-19 Condition (PCC). Serological research data remain a largely untapped resource. Few studies have investigated the potential relationships between post-acute serology and PCC, while accounting for clinical covariates. Methods We compared clinical and serological predictors among COVID-19 survivors with (n=102 cases) and without (n=122 controls) persistent symptoms ≥12 weeks post-infection. We selected four primary serological predictors (anti-nucleocapsid (N), anti-Spike, and anti-receptor binding domain (RBD) IgG titres, and neutralization efficiency), and specified clinical covariates a priori. Results Similar proportions of PCC-cases (66.7%, n=68) and infected-controls (71.3%, n=87) tested positive for anti-N IgG. More cases tested positive for anti-Spike (94.1%, n=96) and anti-RBD (95.1%, n=97) IgG, as compared with controls (anti-Spike: 89.3%, n=109; anti-RBD: 84.4%, n=103). Similar trends were observed among unvaccinated participants. Effects of IgG titres on PCC status were non-significant in univariate and multivariate analyses. Adjusting for age and sex, PCC-cases were more likely to be efficient neutralizers (OR 2.2, 95% CI 1.11 – 4.49), and odds was further increased among cases to report deterioration in quality of life (OR 3.4, 95% CI 1.64 – 7.31). Clinical covariates found to be significantly related to PCC included obesity (OR 2.3, p=0.02), number of months post COVID-19 (OR 1.1, p<0.01), allergies (OR 1.8, p=0.04), and need for medical support (OR 4.1, p<0.01). Conclusion Despite past COVID-19 infection, approximately one third of PCC-cases and infected-controls were seronegative for anti-N IgG. Findings suggest higher neutralization efficiency among cases as compared with controls, and that this relationship is stronger among cases with more severe PCC. Cases also required more medical support for COVID-19 symptoms, and described complex, ongoing health sequelae. More data from larger cohorts are needed to substantiate results, permit subgroup analyses of IgG titres, and explore for differences between clusters of PCC symptoms. Future assessment of IgG subtypes may also elucidate new findings. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement EC is supported by the AI4PH Scholarship Program, funded by CIHR. YG is supported by a Charles Best and Frederick Banting (CGS-Doctoral award) from CIHR (476885). The Stop the Spread Ottawa study is funded by the Canadian Institutes of Health Research (CIHR) (424425), the COVID-19 Immunity Task Force (CITF), and the University of Ottawa. The study extension is funded by the Coronavirus Variants Rapid Response Network (CoVaRR-Net) (156941). CoVaRR-Net is funded by an operating grant from CIHR (FRN 175622). We also acknowledge in-kind support from the NRC Pandemic Response Challenge Program. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics approval was obtained from the The Ottawa Health Science Network Research Ethics Board (Protocol ID Number: 20200481-01H), and access to the data sets was granted by relevant data custodians. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Direct access to the data and analytical files is not permitted without the expressed permission of the approving human research ethics committees and data custodians. Researchers interested in collaboration should contact the corresponding authors.