Early Omicron infection is associated with increased reinfection risk in older adults

A CITF-funded study, published in eClinicalMedicine found that residents of long-term care and retirement homes who had a SARS-CoV-2 infection early in the Omicron wave were more susceptible to get infected with a later Omicron variant than those who had never been infected or who had been infected with pre-Omicron variants. Current vaccination strategies for vulnerable older adults assume that all COVID-19 infections provide enhanced post-infection protection against subsequent infection; however, these data demonstrate this is not true for all variants. The study was a collaboration between Drs. Andrew Costa and Dawn Bowdish (both from McMaster University).

Key findings:

• 133 of 750 residents of long-term care and retirement homes participating in this study (17.7%) had a PCR-confirmed Omicron infection between July and September 2022.
• All participants had received four doses of monovalent mRNA vaccines and had not yet received a bivalent vaccine.
  • Among the 133 participants who had an Omicron infection in this time interval, 37% had received four doses of the Pfizer vaccine, 35% had received four doses of Moderna, and 28% had received a combination Moderna and Pfizer vaccines.
• Of the 617 participants who did not have an Omicron infection between July and September 2022, 71% had not had any prior SARS-CoV-2 infection.
• Among the 133 participants who had an Omicron infection during this interval, 57% had also had a previous Omicron infection.
• Prior to their first Omicron infection, there were no statistically significant differences in vaccine responses between individuals who had never been infected with SARS-CoV-2, who had one Omicron infection or two Omicron infections, implying that there were no innate immune defects in participants who had multiple infections.
• Findings suggest that those who had already had one Omicron infection were more likely to get a second, often 9-29 days after the first.
  • Researchers concluded that this was not attributed to days since fourth vaccination, chronological age, sex assigned at birth, use of immunosuppressive medications, comorbidities, residence type or number of residence outbreaks.
  • Participants with an early Omicron infection had low anti-RBD and anti-spike antibodies after that initial infection.
  • Participants reinfected with a presumed Omicron BA.5 variant also had lower serum neutralizing antibodies to ancestral and Omicron BA.1 strains.
  • Memory T cell responses were similar irrespective of infection history or outcome.

Some individuals, whether they had one or two Omicron infections, mounted similar immune responses, even after similar vaccination histories. The authors suggest that there is significant heterogeneity in this older population, making the prediction of adequate immune responses to multiple vaccine doses or to multiple infections, difficult.

Overall, the data suggest that the increased risk of Omicron reinfection in the BA.5 dominant era after an early Omicron infection (presumed BA.1/2) may have been due to differences in responses to the initial infection and/or other immune-evasive properties of the BA.1/2 variants.

Incidence of SARS-CoV-2 Omicron infection was examined in 750 vaccinated residents of long-term care and retirement homes in Ontario, Canada, within a 75-day period (July to September 2022). Median participant age was 87 years. 64% of participants were female, and 57% were in a long-term care residence. All participants had received four doses of a monovalent mRNA vaccine and had not yet received a bivalent vaccine. Most participants received a combination of mRNA-1273 (Moderna) and BNT162b2 (Pfizer) vaccines (46%). Serum anti-spike and anti-RBD SARS-CoV-2 IgG and IgA antibodies, neutralization titres, and spike-specific T cell memory responses, were examined in a subset of 318 residents within three months of the start of the observation period (i.e., April 1 to June 30, 2022).