Impact of Prior SARS-CoV-2 Infection and Vaccination on COVID-19 Infection among Nursing Home Residents.

There is insufficient evidence regarding the magnitude and durability of the protection conferred by the combined effect of natural immunity after SARS-CoV-2 infection and vaccine-induced immunity among nursing home residents (NHRs), a frail and vulnerable population.1Morciano M. Stokes J. Kontopantelis E. et al.Excess mortality for care home residents during the first 23 weeks of the COVID-19 pandemic in England: a national cohort study.BMC Med. 2021; 19: 71Crossref PubMed Scopus (48) Google Scholar,2Costa A.P. Manis D.R. Jones A. et al.Risk factors for outbreaks of SARS-CoV-2 infection at retirement homes in Ontario, Canada: a population-level cohort study.CMAJ (Can Med Assoc J). 2021; 193: E672-E680Crossref PubMed Scopus (9) Google Scholar In this study, we investigated the effectiveness of licensed mRNA COVID-19 vaccines in preventing COVID-19 infections in NHRs taking into account the presence of previous SARS-CoV-2 infection. This is a retrospective study of a cohort of patients living in nursing homes in our area based on data from the electronic database and health records of our public health service. Only patients aged >60 years were included. We monitored nonvaccinated participants from the beginning of the vaccination campaign until the first dose of vaccine plus 14 days, or death, or the end of the study (January 31, 2022). Those with 1 dose were then switched to "1 vaccine dose" status. We monitored participants with 1 dose from the day they received the first dose plus 14 days until the date of the second dose of vaccine, or death or the end of the study, and those who received a second dose were switched to the "2 vaccine doses" status. We monitored participants with 2 doses from the day they received the second dose until the date of the third dose, or death or the end of the study, and those with a third dose were switched to "3 vaccine doses" status. Finally, participants with 3 doses were monitored from the day they received the third dose until death or the end of the study. We thus treated exposure as time-varying, and a single participant can be included in all 4 statuses (unvaccinated, 1-dose, 2-dose, and 3-dose). Outcome of this study was being positive SARS-CoV-2 infection laboratory-confirmed by a positive result on the reverse transcriptase–polymerase chain reaction assay or a positive antigen test between March 1, 2020, and January 31, 2022. From March 1, 2020, to July 31, 2020, positive IgM or IgG antibody tests performed because of patients displaying symptoms of the disease or having had contact with a positive case were also included in the sample. All positives from each patient were collected if the difference between the date of one positive and the next was ≥120 days. Prior to the vaccination period, the incidence of COVID-19 infection was of 11.44 per 10,000 person-days. Table 1 shows COVID-19 infection according to vaccination status and previous COVID-19 infection for unvaccinated, first, second, and third dose among NHRs. The COVID-19 infection rate per 10,000 person-days for unvaccinated individuals was 11.29, falling after receipt of 1 vaccination dose (9.03) and even more sharply following the second dose (2.19), although it rose again at the time of the third dose (17.73), which also coincided with the appearance of the Omicron variant. The adjusted HR for COVID-19 infection in the 2-dose status compared to the nonvaccinated status was HR = 0.42 (P = .0006). With regard to the effect of prior COVID-19 infection on new infection, the infection rate was much lower for NHRs who had previously had COVID-19. This result was reflected in all adjusted HRs (P < .0001) in all vaccination statuses.Table 1Number and Incidence Rates for COVID-19 According to First, Second, and Third Vaccination Dose Status Among Nursing Home ResidentsStatusPopulationCasesExposure Person-DaysExposure Days (Mean)Rate per 10,000 Person-DaysAdjusted Hazard Ratio (95% CI)∗Adjusted for sex, age, and comorbidities.P Value∗Adjusted for sex, age, and comorbidities.Unvaccinated17,475809716,78741.0211.29Ref.— No previous COVID-1913,014758558,11742.8913.58Ref.— Previous COVID-19446151158,67035.573.210.21 (0.16-0.28)<.0001Vaccinated: 1 dose, from day 1416,719120132,8267.949.031.08 (0.64-1.82).77 No previous COVID-1911,87211692,2727.7712.57Ref.— Previous COVID-194847440,5548.370.990.08 (0.03-0.21)<.0001Vaccinated: 2 doses, from second dose date16,5188053,672,524222.332.190.42 (0.25-0.69).0006 No previous COVID-1911,6647152,564,148219.832.79Ref.— Previous COVID-194854901,108,376228.340.810.31 (0.25-0.38)<.0001Vaccinated: 3 doses, from third dose date13,10826491,494,306114.0017.730.41 (0.23-0.70).0013 No previous COVID-1987212122985,174112.9721.54Ref.— Previous COVID-194387527509,132116.0510.350.46 (0.41-0.50)<.0001Ref., referent.Rate per 10,000 person-days is calculated by dividing the number of observed events within a period by the number of days of exposure, multiplied by 10,000. "Exposure person-days are calculated as the sum of the days each patient is in the corresponding vaccination status until the next possible vaccination status, or outcome, or death, or end of study."Adjusted hazard ratio (95% CI) of those vaccinated with 2 doses vs. 1 dose from day 14: 0.39 (0.30-0.49), P < .0001.Adjusted hazard ratio (95% CI) of those vaccinated with 3 doses vs. 2 doses: 0.97 (0.68-1.40), P = .8900.∗ Adjusted for sex, age, and comorbidities. Open table in a new tab Ref., referent. Rate per 10,000 person-days is calculated by dividing the number of observed events within a period by the number of days of exposure, multiplied by 10,000. "Exposure person-days are calculated as the sum of the days each patient is in the corresponding vaccination status until the next possible vaccination status, or outcome, or death, or end of study." Adjusted hazard ratio (95% CI) of those vaccinated with 2 doses vs. 1 dose from day 14: 0.39 (0.30-0.49), P < .0001. Adjusted hazard ratio (95% CI) of those vaccinated with 3 doses vs. 2 doses: 0.97 (0.68-1.40), P = .8900. This real-world study, conducted among 17,475 NHRs, shows evidence of increased protection from booster vaccine dose and hybrid immunity against severe COVID-19 disease, although the effectiveness against infection has decreased over time due to waning immunity and the immune evasion of new SARS-CoV-2 variants.3Hirabara S.M. Serdan T.D.A. Gorjao R. et al.SARS-COV-2 variants: differences and potential of immune evasion.Front Cell Infect Microbiol. 2022; 11: 781429Crossref PubMed Scopus (95) Google Scholar During our study period, vaccine protection against COVID-19 infection was modest. Both natural infection immunity and first-generation vaccines failed to protect against the transmission of SARS-CoV-2. The finding of modest vaccine effectiveness against infection after 3 doses may be attributed to the Omicron variant, which exhibits a higher transmissibility and infectiveness, and was predominant during the period following this third vaccination.4Muhsen K. Maimon N. Mizrahi A. et al.Effects of BNT162b2 covid-19 vaccine booster in long-term care facilities in Israel.N Engl J Med. 2022; 386: 399-401Crossref PubMed Scopus (21) Google Scholar, 5Accorsi E.K. Britton A. Fleming-Dutra K.E. et al.Association between 3 doses of mRNA COVID-19 vaccine and symptomatic infection caused by the SARS-CoV-2 omicron and delta variants.JAMA. 2022; 327: 639-651Crossref PubMed Scopus (329) Google Scholar, 6Butt A.A. Talisa V.B. Shaikh O.S. Omer S.B. Mayr F.B. Relative vaccine effectiveness of a SARS-CoV-2 mRNA vaccine booster dose against the omicron variant.Clin Infect Dis. 2022; 75: 2161-2168Crossref PubMed Scopus (11) Google Scholar Other factors of influence might also include the relaxation of preventative measures and changes in behavior among vaccinated individuals. This protection was much more striking among patients who had had a COVID-19 infection prior to vaccination, for all vaccination statuses. We found this hybrid immunity even after a single dose. These results have also been reflected by other authors.7Hall V. Foulkes S. Insalata F. et al.Protection against SARS-CoV-2 after covid-19 vaccination and previous infection.N Engl J Med. 2022; 386: 1207-1220Crossref PubMed Scopus (209) Google Scholar, 8Hammerman A. Sergienko R. Friger M. et al.Effectiveness of the BNT162b2 vaccine after recovery from covid-19.N Engl J Med. 2022; 386: 1221-1229Crossref PubMed Scopus (56) Google Scholar, 9Hui D.S. Hybrid immunity and strategies for COVID-19 vaccination.Lancet Infect Dis. 2023; 23: 2-3Abstract Full Text Full Text PDF PubMed Google Scholar Additionally, vaccination and previous infection may have an effect reducing some adverse outcomes, as hospitalization and mortality.6Butt A.A. Talisa V.B. Shaikh O.S. Omer S.B. Mayr F.B. Relative vaccine effectiveness of a SARS-CoV-2 mRNA vaccine booster dose against the omicron variant.Clin Infect Dis. 2022; 75: 2161-2168Crossref PubMed Scopus (11) Google Scholar,10Havers F.P. Pham H. Taylor C.A. et al.COVID-19-associated hospitalizations among vaccinated and unvaccinated adults 18 years or older in 13 US states, January 2021 to April 2022.JAMA Intern Med. 2022; 182: 1071-1081Crossref PubMed Scopus (27) Google Scholar Previous SARS-CoV-2 episodes before vaccination entail an important reduction in infection, showing a clear hybrid immunity effect. The finding that protection conferred by mRNA vaccines waned in the months after receipt of a third dose reinforces the importance of further consideration of additional doses to optimize protective immunity. We are grateful for the support of the Basque Health Service, Osakidetza, and the Department of Health of the Basque Government, and to Tim Nicholson for English language editing. We also gratefully acknowledge the patients who participated in the study. COVID-Health Basque Country Research Group: Janire Portuondo, Julia Garcia (Basque Government Department of Health); Verónica Tiscar, Amaia Bilbao-Gonzalez, Idoia Castillo (Basurto University Hospital); Susana García-Gutierrez, Jose M. Quintana, Maria J. Legarreta, Ane Villanueva, María Gascón, Nere Larrea, Iratxe Lafuente, Cristóbal Esteban, Amaia Aramburu, Pedro Pablo España, Ane Uranga (Galdakao-Usansolo University Hospital); Irantzu Barrio (Universidad del País Vasco/Euskal Herriko Unibertsitatea); Dae-Jin Lee, Abelardo-Enrique Monsalve-Cobis, Lander Rodríguez (Basque Center for Applied Mathematics).