Department of Infectious Diseases and Hepatology, Medical University of Łódź, 90-549 Łódź, Poland
Anna Moniuszko-Malinowska
Department of Infectious Diseases and Neuroinfections, Medical University of Białystok, 15-089 Białystok, Poland
Katarzyna Sikorska
Department of Tropical Medicine and Epidemiology, Medical University of Gdańsk, 80-210 Gdańsk, Poland
Joanna Wernik
Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, 87-100 Toruń, Poland
Dorota Zarębska-Michaluk
Department of Infectious Diseases, Jan Kochanowski University, 25-369 Kielce, Poland
Łukasz Supronowicz
Department of Infectious Diseases and Hepatology, Medical University of Białystok, 15-089 Białystok, Poland
Barbara Sobala-Szczygieł
Department of Infectious Diseases and Hepatology, Medical University of Silesia, 40-055 Katowice, Poland
Agata Skrzat-Klapaczyńska
Department of Adults’ Infectious Diseases, Hospital for Infectious Diseases, Medical University of Warsaw, 02-091 Warsaw, Poland
Krzysztof Simon
Department of Infectious Diseases and Hepatology, Wrocław Medical University, 51-149 Wrocław, Poland
Anna Piekarska
Department of Infectious Diseases and Hepatology, Medical University of Łódź, 90-549 Łódź, Poland
Piotr Czupryna
Department of Infectious Diseases and Neuroinfections, Medical University of Białystok, 15-089 Białystok, Poland
Małgorzata Pawłowska
Department of Infectious Diseases and Hepatology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, 87-100 Toruń, Poland
Michał Brzdęk
Department of Infectious Diseases, Jan Kochanowski University, 25-369 Kielce, Poland
Jerzy Jaroszewicz
Department of Infectious Diseases and Hepatology, Medical University of Silesia, 40-055 Katowice, Poland
Justyna Kowalska
Department of Adults’ Infectious Diseases, Hospital for Infectious Diseases, Medical University of Warsaw, 02-091 Warsaw, Poland
Marcin Renke
Division of Occupational, Metabolic and Internal Diseases, Institute of Maritime and Tropical Medicine, Faculty of Health Sciences, Medical University of Gdansk, 81-519 Gdynia, Poland
Robert Flisiak
Department of Infectious Diseases and Hepatology, Medical University of Białystok, 15-089 Białystok, Poland
The emergence of a highly transmissible and a more pathogenic B.1.617.2 (delta) variant of SARS-CoV-2 has brought concern over COVID-19 vaccine efficacy and the increased risk of severe breakthrough infections. The objective of this study was to assess the frequency and the clinical characteristics of severe breakthrough COVID-19 cases recorded in 10 Polish healthcare units between 1 June and 31 December 2021, a period during which a rapid surge in the share of B.1.617.2 infections was seen, while a significant number of populations were already fully vaccinated. Overall, 723 individuals who completed the initial vaccination regime (fully vaccinated group) and an additional 18 who received a booster dose were identified—together, they represented 20.8% of all the COVID-19 patients hospitalized during the same period in the same healthcare institutions (0.5% in the case of a group that received a booster dose). Although laboratory and clinical parameters did not differ between both groups, patients who received a booster tended to have lower CRP, IL-6, PCT, and d-dimer levels and they required oxygen therapy less frequently. The most common early COVID-19 symptoms in the studied group were fatigue, cough, fever (>38 °C), and dyspnea. Individuals with no detectable anti-spike IgG antibodies constituted 13%; the odds of being a humoral non-responder to the vaccine were increased in patients aged >70 years. Fully vaccinated patients hospitalized after more than 180 days from the last vaccine dose were significantly older and they were predominantly represented by individuals over 70 years and with comorbidities, particularly cardiovascular disease. Contrary to mRNA vaccines, most patients vaccinated with adenoviral vector vaccines were infected within six months. A total of 102 fatal cases (14% of all deaths among vaccinated individuals; 0.7% in the case of a group that received a booster dose) were recorded, representing 17.6% of all the COVID-19 fatalities recorded in June–December 2021 in the considered healthcare units. The odds of death were significantly increased in men, individuals aged >70 years, patients with comorbidities, and those identified as humoral non-responders to vaccination; in fully vaccinated patients the odds were also increased when the second vaccine dose was given >180 days before the first COVID-19 symptoms. The mortality rate in immunocompromised subjects was 19%. The results indicate that compared to vaccinated individuals, severe COVID-19 and deaths in the unvaccinated group were significantly more prevalent during the B.1.617.2-dominated wave in Poland; and, it highlight the protective role of a booster dose, particularly for more vulnerable individuals.