Three Outbreaks of COVID-19 in a Single Nursing Home over Two Years of the SARS-CoV-2 Pandemic

Long-term care facilities (LTCFs) and nursing homes have experienced high burden from COVID-19. Vaccination prioritized LTCFs in early 2021 and reduced transmission and severe outcomes, yet outbreaks continued despite full vaccination, likely due to emerging variants. Prior studies, including Israeli national data, showed high effectiveness of BNT162b2 in older adults, but effectiveness against infection in NHs declined across pre-Delta, intermediate, and Delta periods. The present study reports three COVID-19 outbreaks in a single nursing home near Belgrade, Serbia, during waves of pre-Alpha (Nov 2020), Delta (Nov 2021), and Omicron (Jan 2022) variants. Objectives were to describe and analyze infection characteristics, transmission, and outcomes among residents and staff in each outbreak, with emphasis on sex-related differences, and to compare pre- and post-vaccination periods to analyze vaccine effectiveness.

Evidence from national and international reports indicated that vaccination reduced infection and severe outcomes in older adults and NH residents; however, outbreaks persisted. An Israeli nationwide study found sustained effectiveness of BNT162b2 in older adults, including those aged 85+. Analyses of 3,862 to 14,917 NHs across the pre-Delta, intermediate, and Delta periods reported declining adjusted effectiveness against infection for mRNA vaccines (approximately 74.7% to 53.1%). Reports also documented NH outbreaks with severe disease and deaths despite high vaccination coverage, reflecting ongoing viral evolution and immune escape. These prior findings provided context for evaluating the three outbreaks across variant waves and vaccination phases in the studied NH.

Design: Retrospective observational study of epidemiological and clinical characteristics across three SARS-CoV-2 outbreak waves in one licensed private nursing home (two buildings; capacity 160; 60–72% occupancy; staff 56–64 with one GP and 13 nurses) in suburban Belgrade. Data sources: Review of medical records for affected individuals, capturing age, sex, resident/staff category, hematology, comorbidities, immunization status, therapy, symptoms, hospitalization, and outcomes; annual and trimester mortality comparisons to prior years. Ethics: Informed consent for serology; approvals EO131/20 and EO138/21 (Institute for Medical Research). Case definition and testing: Outbreak start defined by first resident symptomatic PCR-positive case. During Nov 2020–Feb 2022, combined antigen screening (CHIL COVID-19 Antigen Rapid Test) and confirmatory PCR testing were performed. Swabs collected on-site; PCR at regional labs (Belgrade City Institute of Public Health; Institute of Virology, Vaccines and Sera "Torlak"). Infection control: Ministry-recommended measures; PPE for staff; isolation and cohorting; zoning; movement restrictions; visitor bans; staff work arrangements. Forced quarantine was instituted with first detected cases (initially for both residents and staff; later for residents only once staff were vaccinated). Clinical management: On-site physician with infectious disease specialist oversight; severe cases referred to hospital ICUs. Serology: Subset from outbreak 1 tested for anti-SARS-CoV-2 antibodies at 4–8 weeks and 9–12 weeks post-outbreak. Serum processed immediately on receipt; stored at −80°C. IgM and IgG (anti-RBD spike) measured using MINI VIDAS with VIDAS SARS-CoV-2 IgM and IgG II kits (ELFA method). Positive index ≥1; IgG indices converted to BAU/ml using factor 20.33. Statistical analysis: Normality by Shapiro–Wilk and Kolmogorov–Smirnov. Non-normal data compared by Mann–Whitney; multiple comparisons by Kruskal–Wallis with Dunnett’s post hoc. Parametric data analyzed by t-test and one-way ANOVA with Dunn’s or Tukey’s post hoc; Pearson correlation where appropriate. Prism 6 used. Significance level 5%.

Epidemiology and attack rates: Three outbreaks (Nov 2020; Nov 2021; Jan 2022) totaled 189 infections: 122 residents (64.6%), 67 staff (35.4%). Outbreak-specific involvement: 1) 64/126 residents (50.8%) and 45/64 staff (70.3%); 2) 22/75 residents (29.3%) and 3/40 staff (7.5%); 3) 36/110 residents (32.7%) and 19/56 staff (33.9%). Resident mean age ≈80.9±9 years; staff ≈41.0±12.0 years. Severity and outcomes: Spectrum from asymptomatic to severe; severe resident cases referred to ICUs. Case fatality rates (residents only): 31.2% (20/64) in outbreak 1; 9.1% (2/22) in outbreak 2; 0% in outbreak 3. Comorbidities: Hypertension, DM II, and dementia predominated (e.g., outbreak 1: HTA 75%, DM II 23.4%, dementia 29.7%). Oxygen support frequently used in outbreaks 1–2; minimal in outbreak 3. Mortality analyses: Annual mortality rate increased in 2020 (5.4%), 2021 (4.6%), and early 2022 (4.3% to May) vs. 2019 (3.5%); last trimester of 2020 had significantly more deaths than corresponding trimester in 2015–2019. Hematologic and inflammatory markers: Mean leukocytes, neutrophils, lymphocytes, and platelets within normal ranges across outbreaks; in outbreak 3, males had higher neutrophils and platelets and lower lymphocytes than females (all within normal ranges). NLR elevated in all outbreaks; higher in males in outbreak 3. CRP elevated in all outbreaks; higher in males in outbreak 3. D-dimer elevated in 68.8% (outbreak 1; light elevation). Worse outcomes associated with higher leukocytes and neutrophils, lower lymphocytes, and higher CRP and LDH; CRP correlated with disease severity (Pearson r^2=0.1177, p=0.0003). Serology (post-outbreak 1): IgG detected in all residents (35/35) and 44/45 staff at first sampling; residents had significantly higher IgG than staff (417.3±273.5 vs 201.9±192.9 BAU/ml; p<0.0001) despite being older. At follow-up, waning observed (loss of IgG in 1/34 residents and 5/36 staff tested), but residents maintained higher IgG than staff (325.7±214.4 vs 137.7±135.6 BAU/ml; p<0.0001). IgM detected in 77.7% residents and 50% staff; tended to increase with symptom severity. Antibody levels tracked with clinical severity (higher IgG in moderate/severe vs mild/asymptomatic). Vaccination coverage: By Feb–Mar 2021, 94.5% of residents and 100% of staff vaccinated (predominantly BBIBP-CorV; residents ~95% BBIBP-CorV; staff 69.6% BBIBP-CorV, 17.9% BNT162b2, 10.7% Gam-COVID-Vac, 1.8% ChAdOx1). Booster offered Aug 2021; received by 69.1% residents (76/110) and 78.6% staff (44/56). Breakthrough and reinfections: Outbreak 2: 22/22 resident cases and 3/3 staff were breakthrough infections. Outbreak 3: 33/36 resident cases and 19/19 staff were breakthroughs; three unvaccinated residents had primary infections. Majority of breakthrough infections occurred after BBIBP-CorV (85.5% of vaccinated infections). Two deaths in outbreak 2 occurred in individuals vaccinated with two doses of BBIBP-CorV. Reinfections: Four in outbreak 2; 23 in outbreak 3 (13 residents, 10 staff). Of 27 total reinfections, 70.4% followed BBIBP-CorV regimens (six after two doses; 13 after three; three after two BBIBP-CorV plus BNT162b2 booster). Four reinfections occurred after three BNT162b2 doses; one after three Gam-COVID-Vac. Reinfections were clinically mild with no severe cases or deaths.

Across two years and three variant waves, the study shows increasing transmissibility and faster NH entry of successive variants (pre-Alpha took ~8.5 months; Delta ~4.5 months; Omicron ~1 month), consistent with higher R0/Rt and immune escape. Pre-vaccination outbreak had high CFR (31.2%) comparable to international reports in NHs. Post-vaccination outbreaks during Delta and Omicron waves saw markedly reduced severity and mortality (CFR 9.1% and 0%), indicating vaccines’ strong protection against severe disease and death despite numerous breakthrough infections, especially during Omicron amid waning immunity. Clinical biomarkers (elevated NLR, CRP, LDH; lymphopenia) were associated with complications and mortality, aligning with prior prognostic literature. Sex-related differences were minimal in older residents across outbreaks; in outbreak 3 males had higher inflammatory markers but without corresponding severe outcomes. Breakthroughs and reinfections were most common in BBIBP-CorV recipients, suggesting comparatively lower protection against infection or greater waning, though vaccines overall remained effective against severe outcomes. Notably, older residents mounted robust humoral responses after infection, with higher IgG levels than younger staff and antibody levels correlating with clinical severity, underscoring preserved immunogenicity in this population.

Preventive quarantine delayed viral entry, but once SARS-CoV-2 entered the facility, transmission could not be fully contained. Vaccination and boosting substantially reduced severe COVID-19 and mortality in subsequent outbreaks despite high numbers of breakthrough infections with newer variants. Older residents demonstrated strong antibody responses after infection, and serological levels correlated with disease severity. While reinfections and breakthroughs, particularly after BBIBP-CorV regimens, were frequent during Delta and Omicron waves, clinical outcomes were largely mild with no deaths post-vaccination. Continued monitoring, timely boosting, and robust infection control remain crucial in NHs. Future research should track long-term immune dynamics and outcomes in this cohort.

Antibody testing was only performed after the first outbreak, limiting assessment of long-term humoral responses across later outbreaks. Hematologic and inflammatory parameters were not available for infected staff for comparison with residents. Some data elements (e.g., variant confirmation) were inferred from national waves rather than individual sequencing. The single-facility design may limit generalizability.