SARS-CoV-2 adaptive immunity in nursing home residents up to eight months after two doses of the Comirnaty® COVID-19 vaccine

There is scant information as to how SARS-CoV-2 antibody and T-cell immune responses elicited by mRNA COVID-19 vaccines evolve in the general population, and in particular in elderly nursing home residents, who are at increased risk of developing severe clinical forms of COVID-19. We read with interest the work by Tré-Hardy and colleagues who reported a significant antibody decrease at around 6 months after full vaccination in healthcare workers, that was more marked in SARS-CoV-2 naïve vaccinees [1]. The authors suggested that in a supply-limited environment, booster dose schemes may be spared for SARS-CoV-2-experienced individuals. The data presented herein extend this observation to elderly nursing home residents. The current prospective cohort study included 680 (478 female; median age, 87 years; range 65–100) of a cohort of 881 nursing home residents initially recruited from a representative sample of Valencian Community nursing homes (n = 13) for assessment of SARS-CoV-2 immune responses at a median of 3 months (3 M) following full-dose Comirnaty® COVID-19 vaccination [2] who were re-examined at a median of 219 days (range, 139–246) after vaccination (7 M). Out of the 680 participants, 238 had been infected by SARS-CoV-2 prior to receiving the first vaccine dose, as recorded in the electronic Valencia Health System Integrated Databases. Two residents contracted the infection (Delta variant, as documented by whole-genome sequencing) between sampling times (3 M and 7 M). The remaining 440 participants were presumably naïve for SARS-CoV-2 at the time of sampling (7 M).Peer reviewe

Cumulative incidence of SARS-CoV-2 infection in the general population of the Valencian Community (Spain) after the surge of the Omicron BA.1 variant

Background Studies investigating the cumulative incidence of and immune status against SARS-CoV-2 infection provide valuable information for shaping public health decision-making. Methods The current cross-sectional, population-based study, conducted in April 2022 in the Valencian Community (VC), recruited 935 participants of all ages. Anti-SARS-CoV-2-Receptor Binding Domain-RBD-total antibodies and anti-Nucleocapsid (N)- IgGs were measured by electrochemiluminescence assays. To account for past SARS-CoV-2 infection the VC microbiology registry (RedMiVa) was interrogated. |Quantitation of neutralizing antibodies (NtAb) against the ancestral and Omicron BA.1 and BA.2 (sub)variants by an S-pseudotyped neutralization assay and for enumeration of SARS-CoV-2-S specific-IFNγ-producing CD4+ and CD8+ T cells by Intracellular Cytokine Staining assay was performed in a subset of participants (n=100 and 137, respectively). Findings The weighted cumulative incidence was 51□9% (95% CI, 48□7–55□1), and was inversely related to age. Anti-RBD total antibodies were detected in 906/931 (97□3%) participants, those vaccinated and SARS-CoV-2-experienced (VAC-ex;=442) displaying higher levels (P<0.001) than vaccinated/naïve (VAC-n;(n=472) and non-vaccinated/experienced (UNVAC-ex; n(n=63). Antibody levels correlated inversely with the time elapsed since receipt of last vaccine dose in VAC-n (Rho, -0□52; 95% CI, -0□59 to -0□45; P<0.001) but not in VAC-ex. NtAbs against Omicron BA.1 were detected in 94%, 75% and 50% of VAC-ex, VAC-n and UNVAC-ex groups, respectively, while in 97%, 84% and 40%, against Omicron BA.2. SARS-CoV-2-S-reactive IFN-γ T cells were detected in 73%, 75%, and 64% for VAC-ex, VAC-n, UNVAC-ex, respectively. Interpretation By April 2022 around half of the VC population had been infected with SARS-CoV-2 and due to extensive vaccination display hybrid immunity. The large percentage of participants with detectable functional antibody and T-cell responses against SARS-CoV-2, which may be cross-reactive to some extent, points towards lower expected severity than in previous waves.We also thank Ana Berenguer, General Director of Analysis and Public Policies of the Presidency of the Generalitat. Eliseo Albert (Juan Rodés Contract; JR20/00011) Estela Giménez (Juan Rodés Contract, JR18/00053) and Ignacio Torres (Río Hortega Contract; CM20/00090) hold contracts funded by the Carlos III Health Institute (co-financed by the European Regional Development Fund, ERDF/FEDER). Ron Geller holds a Ramon y Cajal fellowship from the Spanish Ministry of Economics and Competitiveness (RYC-2015-17517).N

SARS-CoV-2 adaptive immunity in nursing home residents following a third dose of the Comirnaty® COVID-19 vaccine

A third Comirnaty® vaccine dose increased SARS-CoV-2-receptor binding domain antibody levels (median of 93-fold) and neutralizing antibody titers against Wuhan-Hu-1 (median, 57-fold), Beta (median, 22-fold), Delta, (median, 43-fold) and Omicron (median, 8-fold) variants, particularly in SARS-CoV-2-naïve individuals, but had a negligible impact on S-reactive T-cell immunity in nursing home residents.Peer reviewe

SARS-CoV-2 Delta-variant breakthrough infections in nursing home residents at midterm after Comirnaty® COVID-19 vaccination

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Delta variant break-through infections in nursing home residents following vaccination with Comirnaty®COVID‐19 vaccine were characterized. In total, 201 participants (median age, 87 years;range, 64–100; 133 female) from two nursing homes in the Valencian community (Spain)were included. SARS‐CoV‐2‐Spike (S) antibody responses were determined by a lateralflow immunocromatography (LFIC) assay and by quantitative electrochemiluminescentassay in LFIC‐negative participants. SARS‐CoV‐2‐S‐IFNγT cells were enumerated by flowcytometry in 10 participants. Nasopharyngeal SARS‐CoV‐2 RNA loads were quantified byreal‐time polymerase chain reaction assays. Vaccine breakthrough COVID‐19 due to theDelta variant occurred in 39 residents (median age, 87 years; range, 69–96; 31 female) ata median of 6.5 months after vaccination (nine requiring hospitalization). Breakthroughinfections occurred at a higher rate(p< 0.0001) in residents who had not been previouslyinfected with SARS‐CoV‐2 (naïve) (33/108; 18%) than in those with prior diagnosis ofSARS‐CoV‐2 infection (experienced) (6/93; 6.4%), and were more likely (p< 0.0001) todevelop in residents who tested negative by LFIC (20/49) at 3 months after vaccinationas compared to their LFIC‐positive counterparts (19/142). Among LFIC‐negativeresidents, a trend towards lower plasma anti‐RBD antibody levels was noticed in thosedeveloping breakthrough infection (p=0.16).SARS‐CoV‐2 RNA loads in nasopharyngealspecimens were lower in SARS‐CoV‐2‐experienced residents (p< 0.001) and in thosetesting positive by LFIC (p=0.13). The frequency of SARS‐CoV‐2‐S‐reactive T cells at3monthswassimilarinLFIC‐negative residents with (n=7) or without (n=3)breakthrough infection. Prior history of SARS‐CoV‐2 infection and detection ofS‐reactive antibodies by LFIC at 3 months is associated with a lower risk of Delta‐variant breakthrough infection in nursing home residents at midterm after Comirnaty®COVID‐19 vaccination.We are grateful to the Vice‐presidency and Ministry of Equality andInclusive Policies of the Valencia Community, the Corporate Associationof Residences and Services for People with Dependency of the ValencianCommunity (AERTE), the Valencia Health System nursing homedepartmental committees, and the staff and residents of the participantnursing homes for their collaboration in developing the ProVaVacprogram. We would also like to thank Ana Berenguer, General Directorof Analysis and Public Policies of the Presidency of the Generalitat.Ignacio Torres (Río Hortega Contract; CM20/00090) and Eliseo Albert(Juan Rodés Contract; JR20/00011) hold contracts funded by the HealthInstitute Carlos III (co‐financed by the European Regional DevelopmentFund, ERDF/FEDER). This study received no public or private funds.Peer reviewe

Geographical and temporal structures of Legionella pneumophila sequence types in comunitat Valenciana (Spain), 1998 to 2013

Legionella pneumophila is an accidental human pathogen associated with aerosol formation in water-related sources. High recombination rates make Legionella populations genetically diverse, and nearly 2,000 different sequence types (STs) have been described to date for this environmental pathogen. The spatial distribution of STs is extremely heterogeneous, with some variants being present worldwide and others being detected at only a local scale. Similarly, some STs have been associated with disease outbreaks, such as ST578 or ST23. Spain is among the European countries with the highest incidences of reported legionellosis cases, and specifically, Comunitat Valenciana (CV) is the second most affected area in the country. In this work, we aimed at studying the overall diversity of Legionella pneumophila populations found in the period from 1998 to 2013 in 79 localities encompassing 23 regions within CV. To do so, we performed sequence-based typing (SBT) on 1,088 L. pneumophila strains detected in the area from both environmental and clinical sources. A comparison with the genetic structuring detected in a global data set that included 20 European and 7 non-European countries was performed. Our results reveal a level of diversity in CV that can be considered representative of the diversity found in other countries worldwide

High-resolution mapping of tuberculosis transmission: Whole genome sequencing and phylogenetic modelling of a cohort from Valencia Region, Spain

Artículo con 20 páginas, 5 figuras, 1 tabla. All the sequence data are deposited in the European Nucleotide Archive under the Bioproject number PRJEB29604 (https://www.ebi.ac.uk/ena/data/view/PRJEB29604) and the accession numbers ERR2099780 (https://www.ebi.ac.uk/ena/data/search?query=ERR2099780) and ERR2099784 (https://www.ebi.ac.uk/ena/data/search?query=ERR2099784).BACKGROUND: Whole genome sequencing provides better delineation of transmission clusters in Mycobacterium tuberculosis than traditional methods. However, its ability to reveal individual transmission links within clusters is limited. Here, we used a 2-step approach based on Bayesian transmission reconstruction to (1) identify likely index and missing cases, (2) determine risk factors associated with transmitters, and (3) estimate when transmission happened. METHODS AND FINDINGS: We developed our transmission reconstruction method using genomic and epidemiological data from a population-based study from Valencia Region, Spain. Tuberculosis (TB) incidence during the study period was 8.4 cases per 100,000 people. While the study is ongoing, the sampling frame for this work includes notified TB cases between 1 January 2014 and 31 December 2016. We identified a total of 21 transmission clusters that fulfilled the criteria for analysis. These contained a total of 117 individuals diagnosed with active TB (109 with epidemiological data). Demographic characteristics of the study population were as follows: 80/109 (73%) individuals were Spanish-born, 76/109 (70%) individuals were men, and the mean age was 42.51 years (SD 18.46). We found that 66/109 (61%) TB patients were sputum positive at diagnosis, and 10/109 (9%) were HIV positive. We used the data to reveal individual transmission links, and to identify index cases, missing cases, likely transmitters, and associated transmission risk factors. Our Bayesian inference approach suggests that at least 60% of index cases are likely misidentified by local public health. Our data also suggest that factors associated with likely transmitters are different to those of simply being in a transmission cluster, highlighting the importance of differentiating between these 2 phenomena. Our data suggest that type 2 diabetes mellitus is a risk factor associated with being a transmitter (odds ratio 0.19 [95% CI 0.02-1.10], p < 0.003). Finally, we used the most likely timing for transmission events to study when TB transmission occurred; we identified that 5/14 (35.7%) cases likely transmitted TB well before symptom onset, and these were largely sputum negative at diagnosis. Limited within-cluster diversity does not allow us to extrapolate our findings to the whole TB population in Valencia Region. CONCLUSIONS: In this study, we found that index cases are often misidentified, with downstream consequences for epidemiological investigations because likely transmitters can be missed. Our findings regarding inferred transmission timing suggest that TB transmission can occur before patient symptom onset, suggesting also that TB transmits during sub-clinical disease. This result has direct implications for diagnosing TB and reducing transmission. Overall, we show that a transition to individual-based genomic epidemiology will likely close some of the knowledge gaps in TB transmission and may redirect efforts towards cost-effective contact investigations for improved TB control.IC was supported by European Research Council (638553-TB-ACCELERATE), the Ministerio de Economía y Competitividad (SAF2016-77346-R). CC and YX were supported by the Engineering and Physical Sciences Research Council of the UK (EPSRC EP/K026003/1 (CC) and EPSRC EP/N014529/1 (CC and YX).Peer reviewe