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Direct and indirect effectiveness of mRNA vaccination against SARS-CoV-2 infection
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in long-term care facilities in Spain
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Susana Monge
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, Carmen Olmedo
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, Belén Alejos, María Fé Lapeña
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, María José Sierra
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*,
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Aurora Limia
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* and the COVID-19 registries study group.
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1
Centre for the Coordination of Alerts and Health Emergencies, General Directorate of
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Public Health, Ministry of Health.
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2
Vaccines division, General Directorate of Public Health, Ministry of Health.
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3
Data analytics department, General Directorate of Digital Health and National Health
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Service Information Systems, Ministry of Health.
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* These persons contributed equally to this work.
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Corresponding author:
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Susana Monge
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smonge@mscbs.es
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Conflicts of interest: authors declare no support from any organisation for the
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submitted work; no financial relationships with any organisations that might have an
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interest in the submitted work in the previous three years, no other relationships or
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activities that could appear to have influenced the submitted work.
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Contributions: SM, CO, MJS and AL conceived the idea for the study. SM and CO
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designed the analysis which was performed by SM with help from BA, support from
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MFL and under the supervision of MJS and AL. All authors participated in the
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interpretation of results and critically reviewed the content of the manuscript.
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. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprintthis version posted April 15, 2021. ; https://doi.org/10.1101/2021.04.08.21255055doi: medRxiv preprint
NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
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Funding: This work did not receive any specific grant from funding agencies in the
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public, commercial, or not-for-profit sectors.
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Members of the COVID-19 registries study group: David Moreno, Manuel Méndez
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Díaz, Ismael Huerta González, Antonia Mª Galmes Truyol, Ana Barreno Estévez,
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Valvanuz García Velasco, Mª Jesús Rodríguez Recio, José Sacristán, Montserrat
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Martínez Marcos, Eliseo Pastor Villalba , María José Macías Ortiz, Ana García Vallejo,
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Sara Santos Sanz, Rocío García Pina , Aurelio Barricarte Gurea, Rosa Sancho Martínez,
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Eva María Ochoa, Mauricio Vázquez Cantero, Atanasio Gómez Anés, María Jesús
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Pareja Megía, Yolanda Castán, Manuel Roberto Fonseca Álvarez, Antonia Salvà Fiol,
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Hilda Sánchez Janáriz, Luz López Arce, María Ángeles Cisneros Martín, José Sacristán,
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Frederic Jose Gibernau, Cesar Fernandez Buey, Katja Villatoro Bongiorno, Francisco Javier
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Rubio García, Fernando Santos Guerra, Jenaro Astray Mochales, Francisco Javier
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Francisco Verdu, Isabel García Romero, Rosa Oriza Bernal, Tomás Gómez Pérez, Salomé
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Hijano Villegas, Sergio Román Soto, Virgilio Yagüe Galaup, Mercedes Alfaro Latorre,
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Marta Aguilera Guzmán, Belén Crespo Sánchez-Eznarriaga, Montserrat Neira León,
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Noemí Cívicos Villa.
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. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprintthis version posted April 15, 2021. ; https://doi.org/10.1101/2021.04.08.21255055doi: medRxiv preprint
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Abstract
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Objectives To estimate indirect and total (direct plus indirect) effects of COVID-19
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vaccination in residents in long-term care facilities (LTCF).
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Design Registries-based cohort study including all residents in LTCF ≥65 years offered
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vaccination between 27 December 2020 and 10 March 2021. Risk of SARS-CoV-2
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infection following vaccination was compared with the risk in the same individuals in a
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period before vaccination. Risk in non-vaccinated was also compared to a period
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before the vaccination programme to estimate indirect protection. Standardized
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cumulative risk was computed adjusted by previous documented infection (before the
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start of follow-up) and daily-varying SARS-CoV-2 incidence and reproductive number.
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Participants 573,533 records of 299,209 individuals in the National vaccination registry
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were selected; 99.0% had ≥1 vaccine-dose, 99.8% was Pfizer/BioNTech (BNT162b2).
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Residents mean age was 85.9, 70.9% were females. A previous SARS-CoV-2 infection
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was found in around 25% and 13% of participants, respectively, at the time of vaccine
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offer and in the reference period.
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Main outcome measures Documented SARS-CoV-2 infection identified in the National
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COVID-19 laboratory registry.
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Results Total VE was 57.2% (95% Confidence Interval: 56.1%-58.3%), and was highest
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≥28 days after the first vaccine-dose (proxy of ≥7 days after the second dose) and for
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individuals naïve to SARS-CoV-2 [81.8% (81.0%-82.7%)] compared to those with
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previous infection [56.8% (47.1%-67.7%)]. Vaccination prevented up to 9.6 (9.3-9.9)
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cases per 10.000 vaccinated per day; 11.6 (11.3-11.9) if naïve vs. 0.8 (0.5-1.0) if
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previous infection. Indirect protection in the non-vaccinated could only be estimated
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. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprintthis version posted April 15, 2021. ; https://doi.org/10.1101/2021.04.08.21255055doi: medRxiv preprint
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for naïve individuals, at 81.4% (73.3%-90.3%) and up to 12.8 (9.4-16.2) infections
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prevented per 10.000 indirectly protected per day.
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Conclusions Our results confirm the effectiveness of mRNA vaccination in
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institutionalized elderly population, endorse the policy of universal vaccination in this
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setting, including in people with previous infection, and suggest that even non-
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vaccinated individuals benefit from indirect protection.
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Key-words: COVID-19; SARS-CoV-2; vaccination; vaccine effectiveness; long-term care
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facilities; elderly; indirect effects.
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Key messages:
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COIVD-19 vaccination reduced the risk of documented SARS-CoV-2 infection in
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institutionalized elderly by 57.2% (56.1% to 58.3%), which increased to 81.2%
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(80.2% to 82%) for the fully vaccinated.
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In individuals naïve to SARS-CoV-2 vaccination reduced the risk by up to 81.8% and
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averted up to 11.6 cases per 10,000 vaccinated persons per day.
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Those with previous infection also benefited from a risk reduction of 57%, which
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translated in less than 1 infection averted per 10,000 vaccinated persons per day.
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Non-vaccinated individuals living in facilities where the majority (residents and
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staff) had been vaccinated showed a risk reduction similar to those actually
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vaccinated.
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. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprintthis version posted April 15, 2021. ; https://doi.org/10.1101/2021.04.08.21255055doi: medRxiv preprint
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MAIN TEXT
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Introduction
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Since the beginning of the COVID-19 pandemic up to March 7 2021, 18,927 residents in
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long-term care facilities (LTCF) have died in Spain with confirmed COVID-19, and an
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additional 10,492 have died with compatible symptoms [1]. This means a cumulative
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mortality rate of 67 per 1,000 residents, accounting only for confirmed infections. This
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high vulnerability is due to the higher risk of exposure in dependents living in a closed
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institution but also to the higher severity of infection due to advanced age and
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presence of comorbidities. Indeed, one on every 5 cases of SARS-CoV-2 infection died
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in this setting [1].
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COVID-19 vaccination in Spain started on December 27 with the Pfizer/BioNTech
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(BNT162b2) vaccine, for which LTCF -both residents and workers- were the first priority
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group [2]. The vaccination campaign coincided with the third COVID-19 epidemic wave,
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with national 14-day cumulative incidence increasing from less than 250 cases per
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100,000 population by the end of 2020 to more than 1,000 by the end of January 2021
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[3]. Vaccination started in facilities considered at higher risk, such as those that had
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never experienced a COVID-19 outbreak, had higher number of residents or more
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difficulties for implementing prevention and control measures. Vaccination teams
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visited the facilities and vaccination was universal, including those with previous SARS-
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CoV-2 infection. Vaccination was only deferred in people with active infection and,
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inconsistently, in people under quarantine. Acceptance has been very high, with 97.8%
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of all institutionalized persons (any institution type) having received at least one
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vaccine dose, and 88.8% two doses [4].
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. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprintthis version posted April 15, 2021. ; https://doi.org/10.1101/2021.04.08.21255055doi: medRxiv preprint
