Long-term immune changes after COVID-19 and the effect of BCG vaccination and latent infections on disease severity
Status PubMed-not-MEDLINE Jazyk angličtina Země Austrálie Médium electronic-ecollection
Typ dokumentu časopisecké články
PubMed
40584929
PubMed Central
PMC12203121
DOI
10.1002/cti2.70041
PII: CTI270041
Knihovny.cz E-zdroje
- Klíčová slova
- Bacillus Calmette–Guérin (BCG) vaccination, COVID‐19, Toxoplasma, cytomegalovirus, immune cells, sepsis,
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: Several years after the COVID-19 pandemic, the impact of SARS-CoV-2 on immunity and the potential protective role of Bacillus Calmette-Guérin (BCG) vaccination through trained immunity remain a subject of investigation. This study aimed to determine the long-term impact of SARS-CoV-2 on immune cells and the association between BCG vaccination, latent infections and COVID-19 severity and sepsis progression. METHODS: We conducted a prospective analysis of patients who recovered from mild/severe/critical COVID-19 (n = 97, 3-17 months after COVID-19) and sepsis patients (n = 64). First, we assessed the impact of COVID-19 and its severity on immune cell frequencies and expression of functional markers. Further, we analysed plasma titres of anti-Toxoplasma gondii/cytomegalovirus/BCG antibodies and their association with COVID-19 severity and sepsis outcome. To examine monocyte responses to secondary challenge, monocytes isolated from COVID-19 convalescent patients, BCG vaccinated and unvaccinated volunteers were stimulated with SARS-CoV-2 and LPS. RESULTS: Post-COVID-19 patients showed immune dysregulation regardless of disease severity characterised by altered expression of activation and functional markers in myeloid (CD39, CD64, CD85d, CD11b) and lymphoid cells (CD39, CD57, TIGIT). Strikingly, post-critical COVID-19 patients showed elevated expression of CD57 in CD8+ T cells compared to other severity groups. A trend toward improved outcomes in BCG-seropositive COVID-19/sepsis patients was observed, although this may be confounded by age differences between groups. In contrast, the monocyte response to stimulation appeared unaffected by COVID-19 severity. CONCLUSION: These findings highlight the long-term alterations of immune cells in post-COVID-19 patients, emphasising the substantial impact of COVID-19 on immune function.
Department of Biology Faculty of Medicine Masaryk University Brno Czech Republic
Department of Experimental Biology Faculty of Science Masaryk University Brno Czech Republic
Institute of Hematology and Blood Transfusion Prague Czech Republic
International Clinical Research Center Faculty of Medicine Masaryk University Brno Czech Republic
International Clinical Research Center St Anne's University Hospital Brno Czech Republic
Zobrazit více v PubMed
Kratzer B, Gattinger P, Trapin D PubMed
Yin K, Peluso MJ, Luo X PubMed PMC
Taeschler P, Adamo S, Deng Y PubMed PMC
Wen W, Su W, Tang H PubMed PMC
Lage SL, Amaral EP, Hilligan KL PubMed PMC
Netea MG, Giamarellos‐Bourboulis EJ, Dominguez‐Andres J PubMed PMC
Benn CS, Netea MG, Selin LK, Aaby P. A small jab – a big effect: nonspecific immunomodulation by vaccines. Trends Immunol 2013; 34: 431–439. PubMed
Netea MG, Quintin J, van der Meer JW. Trained immunity: a memory for innate host defense. Cell Host Microbe 2011; 9: 355–361. PubMed
Netea MG, Dominguez‐Andres J, Barreiro LB PubMed PMC
Berg MK, Yu Q, Salvador CE, Melani I, Kitayama S. Mandated Bacillus Calmette‐Guérin (BCG) vaccination predicts flattened curves for the spread of COVID‐19. Sci Adv 2020; 6: eabc1463. PubMed PMC
Hegarty PK, Sfakianos JP, Giannarini G, DiNardo AR, Kamat AM. COVID‐19 and Bacillus Calmette‐Guérin: what is the link? Eur Urol Oncol 2020; 3: 259–261. PubMed PMC
O'Neill LAJ, Netea MG. BCG‐induced trained immunity: can it offer protection against COVID‐19? Nat Rev Immunol 2020; 20: 335–337. PubMed PMC
Moorlag S, Taks E, Ten Doesschate T PubMed PMC
Sinha S, Ajayababu A, Thukral H PubMed PMC
Tsilika M, Taks E, Dolianitis K PubMed PMC
Santos AP, Werneck GL, Dalvi APR PubMed PMC
Kuhtreiber WM, Hostetter ER, Wolfe GE PubMed PMC
Pittet LF, Messina NL, Orsini F PubMed PMC
Madsen AMR, Schaltz‐Buchholzer F, Nielsen S PubMed
Koekenbier EL, Fohse K, van de Maat JS PubMed PMC
Ten Doesschate T, van der Vaart TW, Debisarun PA PubMed PMC
Upton CM, van Wijk RC, Mockeliunas L PubMed PMC
Dos Santos PCP, Messina NL, de Oliveira RD PubMed PMC
Pittet LF, Messina NL, Curtis N. BCG to protect against COVID‐19 in health care workers. Reply. N Engl J Med 2023; 389: 191–192. PubMed
Aaby P, Netea MG, Benn CS. Beneficial non‐specific effects of live vaccines against COVID‐19 and other unrelated infections. Lancet Infect Dis 2023; 23: e34–e42. PubMed PMC
Ehmen HG, Luder CGK. Long‐term impact of PubMed PMC
Barton ES, White DW, Cathelyn JS PubMed
Souza MC, Fonseca DM, Kanashiro A PubMed PMC
Quintin J, Cheng SC, van der Meer JW, Netea MG. Innate immune memory: towards a better understanding of host defense mechanisms. Curr Opin Immunol 2014; 29: 1–7. PubMed
Kleinnijenhuis J, Quintin J, Preijers F PubMed PMC
Quintin J, Saeed S, Martens JHA PubMed PMC
Giamarellos‐Bourboulis EJ, Tsilika M, Moorlag S PubMed PMC
Brook B, Harbeson DJ, Shannon CP PubMed PMC
Schaltz‐Buchholzer F, Bjerregard Oland C, Berendsen M PubMed
Andrejcinova I, Blazkova G, Papatheodorou I PubMed PMC
Singer M, Deutschman CS, Seymour CW PubMed PMC
Karakike E, Giamarellos‐Bourboulis EJ, Kyprianou M PubMed PMC
Vuscan P, Kischkel B, Joosten LAB, Netea MG. Trained immunity: general and emerging concepts. Immunol Rev 2024; 323: 164–185. PubMed
Arnaout M. Structure and function of the leukocyte adhesion molecules CD11/CD18. Blood 1990; 75: 1037–1050. PubMed
Pulte ED, Broekman MJ, Olson KE PubMed PMC
Lord JM, Veenith T, Sullivan J PubMed PMC
Chong M, Yin T, Chen R PubMed PMC
Tian J, Ashique AM, Weeks S PubMed
Malengier‐Devlies B, Filtjens J, Ahmadzadeh K PubMed PMC
De Zuani M, Laznickova P, Tomaskova V PubMed PMC
Du RH, Liang LR, Yang CQ PubMed PMC
Brenchley JM, Karandikar NJ, Betts MR PubMed
Files JK, Boppana S, Perez MD PubMed PMC
Ke J, Huang S, He Z, Lei S, Lin S, Duan M. TIGIT regulates T cell inflammation in airway inflammatory diseases. Inflammation 2024; 48: 15–24. PubMed
Nikolich‐Zugich J, Cicin‐Sain L, Collins‐McMillen D PubMed PMC
Wilking H, Thamm M, Stark K, Aebischer T, Seeber F. Prevalence, incidence estimations, and risk factors of PubMed PMC
Kolbekova P, Kourbatova E, Novotna M, Kodym P, Flegr J. New and old risk‐factors for PubMed
Lachmann R, Loenenbach A, Waterboer T PubMed PMC
Svobodova V, Literak I. Prevalence of IgM and IgG antibodies to PubMed
Flegr J. Toxoplasmosis is a risk factor for acquiring SARS‐CoV‐2 infection and a severe course of COVID‐19 in the Czech and Slovak population: a preregistered exploratory internet cross‐sectional study. Parasit Vectors 2021; 14: 508. PubMed PMC
Jankowiak L, Rozsa L, Tryjanowski P, Moller AP. A negative covariation between toxoplasmosis and COVID‐19 with alternative interpretations. Sci Rep 2020; 10: 12512. PubMed PMC
Pappas G, Roussos N, Falagas ME. Toxoplasmosis snapshots: global status of PubMed
Montoya JG, Liesenfeld O. Toxoplasmosis. Lancet 2004; 363: 1965–1976. PubMed
de Castro MJ, Pardo‐Seco J, Martinon‐Torres F. Nonspecific (heterologous) protection of neonatal BCG vaccination against hospitalization due to respiratory infection and sepsis. Clin Infect Dis 2015; 60: 1611–1619. PubMed
Schaltz‐Buchholzer F, Biering‐Sorensen S, Lund N PubMed
Taks EJM, Moorlag S, Netea MG, van der Meer JWM. Shifting the immune memory paradigm: trained immunity in viral infections. Annu Rev Virol 2022; 9: 469–489. PubMed
Silva TF, Concato VM, Tomiotto‐Pellissier F PubMed PMC
de Chaisemartin C, de Chaisemartin L. Bacille Calmette‐Guérin vaccination in infancy does not protect against coronavirus disease 2019 (COVID‐19): evidence from a natural experiment in Sweden. Clin Infect Dis 2021; 72: e501–e505. PubMed PMC
Khoshnood S, Arshadi M, Akrami S PubMed PMC
Organization WH . Clinical management of COVID‐19: interim guidance, 27 May 2020. World Health Organization. 2020. https://iris.who.int/handle/10665/332196 (Accessed May 20, 2025).
