Correlates of protection and viral load trajectories in omicron breakthrough infections in triple vaccinated healthcare workers.

Marking U, Havervall S, Norin NG, Bladh O, Christ W, Gordon M, Ng H, Blom K, Phillipson M, Mangsbo S, Alm JJ, Smed-Sörensen A, Nilsson P, Hober S, Åberg M, Klingström J, Thålin C

Nat Commun 14 (1) 1577 [2023-03-22; online 2023-03-22]

Vaccination offers protection against severe COVID-19 caused by SARS-CoV-2 omicron but is less effective against infection. Characteristics such as serum antibody titer correlation to protection, viral abundance and clearance of omicron infection in vaccinated individuals are scarce. We present a 4-week twice-weekly SARS-CoV-2 qPCR screening in 368 triple vaccinated healthcare workers. Spike-specific IgG levels, neutralization titers and mucosal spike-specific IgA-levels were determined at study start and qPCR-positive participants were sampled repeatedly for two weeks. 81 (cumulative incidence 22%) BA.1, BA.1.1 and BA.2 infections were detected. High serum antibody titers are shown to be protective against infection (p < 0.01), linked to reduced viral load (p < 0.01) and time to viral clearance (p < 0.05). Pre-omicron SARS-CoV-2 infection is independently associated to increased protection against omicron, largely mediated by mucosal spike specific IgA responses (nested models lr test p = 0.02 and 0.008). Only 10% of infected participants remain asymptomatic through the course of their infection. We demonstrate that high levels of vaccine-induced spike-specific WT antibodies are linked to increased protection against infection and to reduced viral load if infected, and suggest that the additional protection offered by pre-omicron SARS-CoV-2 infection largely is mediated by mucosal spike-specific IgA.

Affinity Proteomics Uppsala [Collaborative]

Autoimmunity and Serology Profiling [Collaborative]

PubMed 36949041

DOI 10.1038/s41467-023-36984-1

Crossref 10.1038/s41467-023-36984-1

pmc: PMC10031702
pii: 10.1038/s41467-023-36984-1