Participant demographics and clinical characteristics
A total of 20 recovered COVID-19 patients were recruited into the study (Table 1). All the study participants received at least a single dose of a COVID-19 vaccine (COVISHIELD™, n = 19 or Janssen Ad26.COV2. S, n = 1) as part of the routine vaccination programme. Of the 19 COVISHIELD™-vaccinated adults, 12 received two doses, and 7 received one dose. The median time from the first vaccine dose to laboratory-confirmed breakthrough infection was 138 days (IQR 112–253 days). Of the 12 that received two doses of COVISHIELD™, 42% (n = 5) experienced breakthrough infections after completing both doses and 58% (n = 7) experienced breakthrough infections after the first dose. Although we did not perform SARS-CoV-2 genomic sequencing as part of the study, it’s worth noting that the recruitment period coincided with the third and fourth waves dominated by the Delta and Omicron variants, respectively [18]. Furthermore, none of the study participants experienced severe COVID-19 or hospitalisation during the follow-up period. Additionally, none of them reported any PCR-confirmed SARS-CoV-2 infection during this time.
Table 1. Participant Demographics and site characteristics
Kinetics and magnitude of serum anti-SARS-CoV-2-specific IgG antibodies
We assessed the kinetics of binding anti-SARS-CoV-2 IgG antibodies by measuring the levels of serum anti-RBD, anti-Spike and anti-nucleocapsid-specific IgG antibodies throughout the follow-up period. The levels of anti-RBD and anti-Spike-specific IgG antibodies decreased over time but remained within the levels associated with protection against severe COVID-19 until at least one-year post-hybrid immunity (Fig. 1a-b). A notable waning of anti-nucleocapsid IgG antibodies was observed in the first 150 days post-initial breakthrough infection, followed by a rise in the antibody levels, which peaked at 180 days and gradually waned thereafter (Fig. 2a). Furthermore, individual kinetics of anti-nucleocapsid IgG antibodies indicated a median of 1 peak per individual during the study follow-up period (1 peak [95% CI, 0–1]) (Fig. 2b), which suggested SARS-CoV-2 re-infection. As previously reported [19], the re-infection events were determined by a 2-fold increase in anti-nucleocapsid IgG antibodies between time points. Overall, this indicates that binding IgG antibodies in vaccinated adults induced following breakthrough infection are durable and likely maintained at protective levels through non-severe SARS-CoV-2 re-infections.
Neutralisation breadth of serum anti-SARS-CoV-2-specific IgG antibodies over time
To ascertain the neutralisation breadth of SARS-CoV-2 binding IgG antibodies, we quantified ACE2 IgG inhibiting Spike and RBD antibodies in the sera obtained at 90, 240 and 360 days post-initial breakthrough infection. Anti-ACE2 inhibition IgG antibodies were used as a surrogate of neutralisation capacity. First, we compared the neutralisation capacity of serum anti-RBD and anti-Spike-specific IgG antibodies using ancestral antigens. We found that there was no significant difference in the neutralisation potency across the three time points (Fig. 3a-b). Second, we compared the neutralisation breadth of anti-Spike-specific IgG antibodies against Alpha, Beta, Gamma, and Omicron. We found that the neutralisation breadth was maintained for at least 360 days after initial breakthrough infection (Fig. 3c-e). Additionally, ACE-2 IgG inhibition percentage against Delta, Gamma, Beta, Alpha, and Wild-type was above 90% during the study follow-up period but was less than 80% against Omicron (Fig. 3c-e). Collectively, this data indicate that hybrid immunity generated in the context of an adenovirus-based COVID-19 vaccine and breakthrough infection is not only broadly cross-neutralising but also maintained for at least 360 days.