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