CITF-funded findings on accelerated research in long-term care settings

Studying the immune responses of older Canadians to infections and to vaccines has helped to inform the appropriate timing for booster vaccines in this vulnerable population, especially those living in long-term care (LTC) homes. Wastewater surveillance has also proven to be a useful early detection system for outbreaks in LTC homes (LTCH). Here, members of the CITF Secretariat summarize the results from the five presentations given during the breakout session, “Accelerated research in long-term care settings,” at the CITF Scientific Meeting in Vancouver, March 8-10, 2023.

1. Presenter Professor Zabrina Brumme and CITF PI Dr. Marc Romney: Impact of age and SARS-CoV-2 breakthrough infection on humoral immune responses after three doses of COVID-19 mRNA vaccine

This study cohort was established in December 2020, just as the first British Columbians began receiving their COVID-19 vaccines. The cohort consisted of two groups: 89 younger adults (healthcare workers) with a median age of 41 years, of whom 73% were female, and 62 elder adults (including long-term care residents) with a median age of 79 years, of whom 69% were female. All study participants received three vaccine doses.

• At least three COVID-19 mRNA vaccine doses were needed for antibody levels in older adults to reach equivalence to younger adults.
• The rate of antibody decline was comparable in older and younger adults. By six months after dose three, antibody levels generally declined to below the levels initially induced by two vaccine doses.
• Six months after the third vaccine dose, it was also observed:
• Antibody levels in individuals who got SARS-CoV-2 infection were higher than those induced by three vaccine doses alone.
• Neutralization of Omicron in individuals who got SARS-CoV-2 infection was higher than in individuals who received three vaccine doses alone.
• The ability to neutralize Omicron (BA.1) declined to undetectable levels in 56% of younger adults and 96% of older adults.
• The ability to neutralize Omicron BA.5 after three vaccine doses or after three doses followed by a breakthrough infection was even poorer than the ability to neutralize BA.1 had been for both younger and older adults.

Overall, antibody and neutralization responses against the first-generation COVID-19 mRNA vaccines – and even those generated by SARS-CoV-2 infection – do not neutralize Omicron BA.5 as well as previous variants, supporting the roll-out of bivalent vaccines.

2. Presenter and CITF PI Dr. Sharon Straus, Implementation of a co-created strategy to characterize COVID-19 exposure and optimize wellness in congregate care settings for older adults: The Wellness Hub

The Wellness hub used an integrated knowledge translation approach to estimate the prevalence of SARS-CoV-2 infection and identify risk factors associated with infection in long-term care and retirement homes. This was a retrospective analysis of an observational study using surveillance data on laboratory-confirmed COVID-19 cases (Jan 23 to Dec 13, 2020, prior to COVID-19 vaccines).

• Hardest-hit neighbourhoods (comprising 20% of the population) accounted for 53.9% of community cases, 48.6% of LTCH staff cases, and 42.3% of other health care worker (HCW) cases.
• Congregate setting staff cases were associated with lower-income neighbourhoods, having a higher household density, and having a higher proportion of people working in other essential services.
• A fourth dose of mRNA vaccine resulted in substantially increased PRNT50 titers, assays used to measure neutralizing antibodies, against Omicron in LTC residents.

Overall, the Wellness Hub found different research disciplines can facilitate tailored approaches to linking immunity to interventions, mitigating infection risk, and promoting wellness in high-risk settings.

3. Presenter and CITF PI Dr. Xiaoli (Lilly) Pang and CITF PI Dr. Chris Sikora: Targeted wastewater-based surveillance for COVID-19 outbreaks in the long-term care facilities in Edmonton, Canada

Site-specific wastewater-based surveillance for SARS-CoV-2 started Jan 6, 2021 and was ongoing through Spring 2023. Twelve long-term care facilities in Edmonton participated in this study which concentrated collected wastewater samples for further analysis.

• Positive samples increased from 14.2% in Jan 2021-Aug 2022 to 34.6% in December 2021-Aug 2022, coinciding with the emergence of Omicron.
• Wastewater results were highly correlated to the number of COVID-19 clinical cases.
• Overall, it was observed that wastewater SARS-CoV-2 surveillance is:
  • Sensitive (able to detect even one case in the entire facility)
  • Comprehensive (finding both asymptomatic/pre-symptomatic/symptomatic cases)
  • Non-invasive and unobtrusive
  • Low maintenance (testing the entire facility only requires one sample)
  • Useful for outbreak monitoring

4. Presenter and CITF PI Dr. Lisa Barrett: Long-term care resident SARS-CoV-2 vaccine response is modified by previous infection and CMV coinfection

Study participants were recruited from four LTCs in Nova Scotia. “Low COVID penetrance” LTC residents (N=356) provided samples between wave 2 (Jan 2021, pre-vaccine era) and wave 6 (Aug 2022, three months after dose four).

Of this “Low COVID penetrance” LTC resident cohort, 239 participants were alive at three months post fourth dose. Of these, 105 tested positive and 134 individuals still tested negative for SARS-CoV-2 infection.

• LTC residents with hybrid immunity had increased cell-mediated vaccine responses, with an increase in both spike-specific B and T cells.
• Vaccine-induced B cell responses were not altered by CMV infection.
• Vaccine-induced T-cell responses in SARS-CoV-2-naïve LTC residents were greatest in CMV-positive individuals.

Overall, vaccines have been successful in preventing severe COVID-19 outcomes, including deaths in this frail and vulnerable population.

5. Presenter and CITF PI Dr. Allison McGeer: Antibody responses to vaccine and protection from COVID-19 in residents of long-term care homes

This study compared antibody levels against SARS-CoV-2 after vaccination in residents and staff of LTCs. Dried blood samples from 200 LTC residents were collected several times starting prior to dose one (before Feb 2021) until 14 days after bivalent boosters (until after Oct 2022). Median age of residents was 88 years and 69% were female.

• Two doses of the Moderna vaccine were 3.6 times more effective in terms of SARS-CoV-2 neutralization than two doses of the Pfizer vaccine in LTC residents.
• Seroconversion (development of anti-S levels) after two vaccine doses was 6.9 times higher in staff than in LTC residents. Frail older adults needed more vaccine doses to achieve antibody levels similar to those of younger adults.
• The correlation between antibody titres and protection from infection appears to be variant specific. At least four vaccine doses were required in older adults to protect against Omicron and its subvariants.