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Abstract

Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder related to recurrent infections, as well as a range of non-infectious manifestations including autoimmune and inflammatory disorders. We hypothesized that patients with CVID and different clinical phenotypes would demonstrate alterations in lymphocyte T subsets, including T lymphocytes expressing programmed cell death protein 1 (PD-1), and regulatory T lymphocytes. We performed flow cytometry in two CVID groups: group 1 with infections only, and group 2 with infections and concomitant noninfectious manifestations. Patients were 18–59 years old (mean 35.8 years of age). Increased proportions of CD8+PD-1+ T cells and reduced regulatory T cells were associated with lymphadenopathy. Amount of regulatory T cells correlated with CD8+PD-1+ T lymphocytes (r = 0.54; p = 0.013), and with CRP (r = –0.64; p = 0.004). Forty percent of patients expressed manifestations in addition to infections (group 2), and they had reduction in number of regulatory T cells [8 (3–12) vs. 24 (11–26)/μl; p = 0.034), naive CD4+ T lymphocytes [36 (27–106) vs. 149 (81–283)/μl; p = 0.034], and elevated C-reactive protein (CRP) [5.33 (3.15–8.82) vs. 1 (1–2.16) mg/l; p = 0.003] in comparison to group 1. In conclusion, the amount of CD8+ T cells expressing PD-1 is associated with lymphadenopathy and number of regulatory T cells in patients with CVID. Patients with CVID and non-infectious complications have increased level of inflammation and alterations in regulatory T cells.
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Authors and Affiliations

Ewelina Nowak
1
Joanna Sulicka-Grodzicka
2
Magdalena Strach
1
Karolina Bukowska-Strakova
3
Maciej Siedlar
3
Mariusz Korkosz
2
ORCID: ORCID
Tomasz Grodzicki
1

  1. Department of Internal Medicine and Gerontology, Jagiellonian University Medical College, Kraków, Poland
  2. Department of Rheumatology, Jagiellonian University Medical College, Kraków, Poland
  3. Department of Clinical Immunology, Institute of Pediatrics, Jagiellonian University Medical College, Kraków, Poland
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Abstract

The complex course of the COVID-19 and the distant complications of the SARS-CoV-2 infection still remain an unfaded challenge for modern medicine. The care of patients with the sympto-matic course of COVID-19 exceeds the competence of a single specialty, often requiring a multispecialist approach. The CRACoV-HHS (CRAcow in CoVid pandemic — Home, Hospital and Staff) project has been developed by a team of scientists and clinicians with the aim of optimizing medical care at hospital and ambulatory settings and treatment of patients with SARS-CoV-2 infection. The CRACoV project integrates 26 basic and clinical research from multiple medical disciplines, involving different populations infected with SARS-CoV-2 virus and exposed to infection.
Between January 2021 and April 2022 we plan to recruit subjects among patients diagnosed and treated in the University Hospital in Cracow, the largest public hospital in Poland, i.e. 1) patients admitted to the hospital due to COVID-19 [main module: ‘Hospital’]; 2) patients with signs of infection who have been confirmed as having SARS-CoV-2 infection and have been referred to home isolation due to their mild course (module: ‘Home isolation’); 3) patients with symptoms of infection and high exposure to SARS- CoV-2 who have a negative RT-PCR test result. In addition, survey in various professional groups of hospital employees, both medical and non-medical, and final-fifth year medical students (module: ‘Staff’) is planned.
The project carries both scientific and practical dimension and is expected to develop a multidisciplinary model of care of COVID-19 patients as well as recommendations for the management of particular groups of patients including: asymptomatic patient or with mild symptoms of COVID-19; symptomatic patients requiring hospitalization due to more severe clinical course of disease and organ complications; patient requiring surgery; patient with diabetes; patient requiring psychological support; patient with undesirable consequences of pharmacological treatment.
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Bibliography

1. Duszyński J., Afelt A., Ochab-Marcinek A., Owczuk R., Pyrć K., Rosińska M., Rychard A., Smiatacz T.: Zrozumieć Covid-19. 2020. Polska Akademia Nauk. https://pan.pl/images/2020/opracowanie-covid19-14-09-2020/ZrozumiecCovid19_opracowanie_PAN_interactive.pdf
2. Sydor W.: COVID-19 a zaburzenia krzepnięcia. Medical Research Reviews. ISBN 978–83–65515–97–1.
3. Hu B., Guo H., Zhou P., Zheng-Li S.: Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol. 2021; 19: 141–154. https://doi.org/10.1038/s41579-020-00459-7.
4. Levi M., Thachil J., Iba T., Levye J.H.: Coagulation abnormalities and thrombosis in patients with COVID-19. Lancet Haematol. 2020; 7: e438–e440.
5. Terlecki M., Wojciechowska W., Klocek M., Olszanecka A., Stolarz-Skrzypek K., Grodzicki T., et al.: Association between cardiovascular disease, cardiovascular drug therapy, and in-hospital outcomes in patients with COVID-19: data from a large single-center registry in Poland. Kardiologia Polska. 2021.
6. Undas A., Podolak-Dawidziak M., Pruszczyk P., Windyga J.: Tromboprofilaktyka i leczenie przeciwkrzepliwe u dorosłych chorych hospitalizowanych z powodu COVID-19. 30 marca 2020. https://nil.org.pl/aktualnosci/5395-tromboprofilaktyka-i-leczenie-przeciwkrzepliwe-u-doroslych- chorych-hospitalizowanych-z-powodu-covid-19.
7. Flisiak R., Horban A., Jaroszewicz J., et al.: Zalecenia postępowania w zakażeniach SARS-CoV-2 Polskiego Towarzystwa Epidemiologów i Lekarzy Chorób Zakaźnych, na dzień 26 kwietnia 2021. http://www.pteilchz.org.pl/wp-content/uploads/2021/04/REKOMENDACJE-pl-w-C19-2021-26-04- 2021b.pdf.
8. Lo Bianco G., Di Pietro S., Mazzuca E., et al.: Multidisciplinary Approach to the Diagnosis and In- Hospital Management of COVID-19 Infection: A Narrative Review. Front Pharmacol. 2020 Dec 9; 11: 572168. https://doi.org/10.3389/fphar.2020.572168.
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Authors and Affiliations

Wojciech Sydor
1 2
Barbara Wizner
3
Magdalena Strach
2
Monika Bociąga-Jasik
4 5
Krzysztof Mydel
6
Agnieszka Olszanecka
7
Marek Sanak
8 5
Maciej Małecki
9 5
Jadwiga Wójkowska-Mach
10
Robert Chrzan
11
Aleksander Garlicki
4 5
Tomasz Gosiewski
12 5
Marcin Krzanowski
13 5
Jarosław Surowiec
14 5
Stefan Bednarz
15 5
Marcin Jędrychowski
16 5
Tomasz Grodzicki
3 5
The CraCoV-HHS Investigators

  1. Center for Innovative Therapies, Clinical Research Coordination Center, University Hospital in Cracow, Poland
  2. Department of Rheumatology and Immunology, Jagiellonian University Medical College, Cracow, Poland
  3. Department of Internal Medicine and Gerontology, Jagiellonian University Medical College, Cracow, Poland
  4. Department of Infectious and Tropical Diseases, Jagiellonian University Medical College, Cracow, Poland
  5. Steering Committee of the CRACoV-HHS
  6. Deputy Director for Coordination and Development, University Hospital in Cracow, Poland
  7. Department of Cardiology, Interventional Electrocardiology and Hypertension, Jagiellonian University Medical College, Cracow, Poland
  8. 2nd Department of Internal Medicine, Jagiellonian University Medical College, Cracow, Poland
  9. Department of Metabolic Diseases and Diabetology, Jagiellonian University Medical College, Cracow, Poland
  10. Chair of Microbiology, Medical Faculty, Jagiellonian University Medical College, Cracow, Poland
  11. Department of Radiology, Jagiellonian University Medical College, Cracow, Poland
  12. Department of Molecular Medical Microbiology, Chair of Microbiology, Medical Faculty, Jagiellonian University Medical College, Cracow, Poland
  13. Department of Nephrology and Dialysis Unit, Jagiellonian University Medical College; Deputy Medical Director, University Hospital in Cracow, Poland
  14. Head of Quality, Hygiene and Infection Control Section at University Hospital in Cracow, Poland
  15. Head of Primary Care Unit at University Hospital in Cracow, Poland
  16. Director of University Hospital in Cracow, Poland

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