Correlates of protection, viral load trajectories and symptoms in BA.1, BA.1.1 and BA.2 breakthrough infections in triple vaccinated healthcare workers

Background Booster vaccine doses offer protection against severe COVID-19 caused by omicron but are less effective against infection. Characteristics such as serological correlates of protection, viral abundance, and clearance of omicron infection in triple vaccinated individuals are scarce. Methods We conducted a 4-week twice-weekly SARS-CoV-2 qPCR screening shortly after an mRNA vaccine booster in 368 healthcare workers. Spike-specific IgG levels and neutralization titers were determined at study start. qPCR-positive participants were sampled repeatedly for two weeks and monitored for symptoms. Result In total 81 (cumulative incidence 22%) omicron infections were detected, divided between BA.1, BA.1.1 and BA.2. Increasing post-booster antibody titers were protective against infection (p<0.05), linked to reduced viral load (p<0.01) and time to viral clearance (p<0.05). Only 10% of infected participants remained asymptomatic through the course of their infection. Viral load peaked at day 3 and live virus could be detected for up to 9 days after first PCR-positive sample. Presence of symptoms correlated to elevated viral load (p<0.0001), but despite resolution of symptoms most participants showed Ct levels <30 at day 9. No significant differences were observed for viral load and time to viral clearance between BA.1, BA.1.1 and BA.2 infected individuals. Conclusion We report a high incidence of omicron infection despite recent booster vaccination in triple vaccinated individuals. Increasing levels of vaccine-induced spike-specific WT antibodies entail increased protection against infection and reduce viral load if infected. High viral load and secretion of live virus for up to nine days may facilitate transmission in a triple vaccinated population. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was funded by Jonas & Christina af Jochnick foundation (CT) Lundblad family foundation (CT); Region Stockholm (CT); Knut and Alice Wallenberg foundation (CT, JK); Jonas Soderquists scholarship (CT); Science for Life Laboratory (PN); Erling-Persson family foundation (SoH); Center for Innovative Medicine (JK, KB); and Swedish Research Council (JK). The funders above had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. ### 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: The study was approved by the Swedish Ethical Review Authority (dnr 2020-01653) and conducted in accordance with the declaration of Helsinki. Written informed consent was obtained from all study participants. 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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors