key: cord-0697773-ar16vkla
authors: Albert, Eliseo; Burgos, Javier S.; Peiró, Salvador; Salas, Dolores; Vanaclocha, Hermelinda; Giménez, Estela; Limón, Ramón; Alcaraz, María Jesús; Sánchez-Payá, José; Díez-Domingo, Javier; Navarro, David
title: Immunological response against SARS-CoV-2 following full-dose administration of Comirnaty® COVID-19 vaccine in nursing home residents
date: 2021-10-05
journal: Clin Microbiol Infect
DOI: 10.1016/j.cmi.2021.09.031
sha: b226435a61b0a1cb5554729f52068409b5b82529
doc_id: 697773
cord_uid: ar16vkla

OBJECTIVES: The current study was aimed at examining SARS-CoV-2 immune responses following two doses of Comirnaty® COVID-19 vaccine among elderly people in nursing home residences. METHODS: A prospective cohort study in a representative sample from Valencia nursing homes (n=881; males: 271, females 610; median age, 86 years) was recruited using a random one-stage cluster sampling approach. A lateral flow immunocromatography device (LFIC) (OnSite COVID-19 IgG/IgM Rapid Test; CTK BIOTECH, Poway, CA, USA) was used as the front-line test for detecting SARS-CoV-2-Spike(S)-specific antibodies in whole blood obtained by fingerstick. Residents returning negative LFIC results underwent venipuncture and testing for presence of SARS-CoV-2-S-reactive antibodies and T cells by the Roche Elecsys® Anti-SARS-CoV-2 S (Roche Diagnostics, Pleasanton, CA, USA), the LIAISON® SARS-CoV-2 TrimericS IgG assay (Diasorin S.p.A, Saluggia, Italy), and by flow cytometry, respectively. RESULTS: The SARS-CoV-2-S antibody detection rate in nursing home residents was 99.6% (283/289) and 98.3% (587/597) for SARS-CoV-2 recovered and naïve residents, respectively, within a median of 99 days (range, 17-125 days) after full vaccination. Three out of five residents lacking SARS-CoV-2-S antibodies had detectable S-reactive CD8(+) and/or CD4(+) T cells. 50/50 and 40/50 participants with detectable SARS-CoV-2 antibodies also had SARS-CoV-2-S-reactive IFN-γ-producing CD4(+) and CD8(+) T cells, respectively. CONCLUSION: The Comirnaty® COVID-19 vaccine is highly immunogenic in nursing home residents.

Older people have been prioritized for vaccination against SARS-CoV-2 because of their 80 increased risk of severe COVID-19 [1] . Deployment of SARS-CoV-2 messenger RNA 81 to local law and regulations, the publication of the data is exempt from the approval of a 111 research ethics committee. Personal data from nursing homes and residents were 112 processed in accordance with European data protection regulations. 113

Participants were scheduled to be tested for presence of SARS-CoV-2-Spike (S)-specific 115 Biosciences, San Jose, CA) as previously described [6, 12] . Likewise, randomly selected 142 whole blood specimens from residents (n=50) testing LFIC negative/ECLIA positive 143 were processed for T-cell immunity analysis. 144

Frequency comparisons for categorical variables were carried out using the Fisher exact 146 test. Differences between medians were compared using the Mann-Whitney U-test. Two-147 sided exact P-values were reported. The Spearman Rank test was used for correlation 148 analyses between continuous variables. A P-value <0.05 was considered statistically 149 significant. The analyses were performed using SPSS version 20.0 (SPSS, Chicago, IL, 150 USA). 151

One small nursing home (n = 12) failed to provide blood specimens from residents testing 153 negative by LFIC and was excluded; in turn, 36 randomly selected individuals from the 154 additional nursing home incorporated for potential losses were included, leaving a total Experiments performed using plasma specimens with known SARS-CoV-2-S-reactive 171 antibody levels (0, 50, 250 and 1,000 IU/ml), as quantitated by the Roche ECLIA, 172 revealed that IgG test band intensity increased in parallel with antibody levels ( Figure 2 ). 173

IgG LFIC results were thus graded 03+, as detailed in the methods section. 174

Overall, as shown in Table 2 important. In effect, among residents testing negative by LFIC, the Roche ECLIA assay 274 returned more positive results than the Diasorin CLIA, which may reflect between-assay 275 differences in analytical sensitivity but could also be related to the nature of the binding 276 antigen in the assays (RBD vs. trimeric S protein, respectively). 277

The current study has several limitations. First, use of an LFIC assay for serological 278 testing in most residents precluded precise quantitation of antibody levels. Moreover, the 279 possibility that some of the positive LFIC results were false-positive ones (specificity, 280 99%) cannot be ruled out as these were not confirmed by ECLIA or CLIA. Second, no 281 control group was included. Third, no pre-vaccination specimens were available for 282 analyses; this precluded assessing the booster effect in those with prior SARS-CoV-2 283 infection. Fourth, some residences submitted red-top tubes for serum collection instead, 284 which prevented T-cell immunity analyses. Fifth, testing for presence of SARS-CoV-2-285 S-reactive T cells with functional specificities other than IFN-γ production was not 286 conducted. Sixth, we cannot rule out that some participants herein categorized as SARS-287

CoV2 naïve had indeed experienced asymptomatic or paucisymtomatic SARS-CoV-2 288 infection that were missed. Nonetheless, the sample size stands out as a major strength of 289 this study. Community within the study period, residents suspected of having COVID-19 were tested 377 within 24 h after the onset of symptoms for the presence of SARS-CoV-2 RNA in the 378 upper respiratory tract by RT-PCR. In addition, systematic testing of asymptomatic 379 residents was triggered by the occurrence of symptomatic cases and also conducted within 380 J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f Table 3 

CD8 + T cells detectable responses/ median frequency (range)

Efficacy and safety of COVID-19 vaccines in 320 older people

Interim Estimates of Vaccine Effectiveness of Pfizer-BioNTech and Moderna COVID

Vaccines Among Health Care Personnel -33

CoV-2 Infection among mRNA-Vaccinated and Unvaccinated Nursing Home Residents

Weak humoral 329 immune reactivity among residents of long-term care facilities following one dose of the 330 BNT162b2 mRNA COVID-19 vaccine

B and T cell 337 immune responses elicited by 1 the BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine 338 in nursing home residents

Safety 341 and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates

Data Resource Profile: The Valencia Health System Integrated Database 345 (VID)

Evaluation of 11 SARS-CoV-2 antibody tests by using samples from patients with 348 defined IgG antibody titers

Suitability of two rapid lateral flow immunochromatographic assays for predicting

SARS-CoV-2 neutralizing activity of sera

Establishment of the WHO International 353 Standard and Reference Panel for anti-SARS-CoV-2 antibody

(phytohemagglutinin) and isotype controls were used. Cells were then washed, 408 resuspended in 200 μL of 1% paraformaldehyde in PBS, and analyzed within 2 h on a 409FACSCanto flow cytometer using DIVA v8 software (BD Biosciences 410 Immunocytometry Systems, San Jose, CA). CD3 + /CD8 + or CD3 + /CD4 + events were 411 gated and then analyzed for IFN-γ production. All data were corrected for background 412 IFN-γ production (FITC-labelled isotype control antibody) and expressed as a percentage 413 of total CD8 + or CD4 + T cells. The asterisk symbols indicate that whole-blood specimens 414 either were not available or were not processed from all participants; in fact, a total of 5 415 subjects lacking antibody responses could be examined, whereas, a total of 50 individuals 416 among those with detectable antibody responses were randomly selected for T-cell 417 immunity testing. 418