Nejvíce citovaný článek - PubMed ID 34913354
Inhibitory immune checkpoint molecules and exhaustion of T cells in COVID-19
Coronavirus disease 2019 (COVID-19) is a highly contagious viral disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It can manifest as mild to severe flu-like and non-flu-like symptoms and signs, which are associated with immune dysfunction and increased mortality. The findings from COVID-19 patients imply a link between immune system abnormalities such as impaired T-cell responses or cytokine imbalances and increased risk for worse clinical outcomes, which has not been fully understood. Owing to the regulatory role of inhibitory immune checkpoints during COVID-19 infection, this review summarizes the available studies concerning the TIM3 as a relatively less characterized immune checkpoint in COVID-19 patients.
- Klíčová slova
- Biomarker, COVID-19, Immune checkpoint, Infection, TIM3, Virus,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
SARS-CoV-2 infection, which causes the respiratory disease COVID-19, has spread rapidly from Wuhan, China, since 2019, causing nearly 7 million deaths worldwide in three years. In addition to clinical risk factors such as diabetes, hypertension, and obesity, genetic variability is an important predictor of disease severity and susceptibility. We analyzed common polymorphisms within the LZTFL1 (rs11385942) and ABCA3 (rs13332514) genes in 519 SARS-CoV-2-positive subjects (164 asymptomatic, 246 symptomatic, and 109 hospitalized COVID-19 survivors) and a population-based control group (N?=?2,592; COVID-19 status unknown). Rare ABCA3 AA homozygotes (but not A allele carriers) may be at a significantly increased risk of SARS-CoV-2 infection [P?=?0.003; OR (95 % CI); 3.66 (1.47-9.15)]. We also observed a borderline significant difference in the genotype distribution of the LZTFL1 rs11385942 polymorphism (P?=?0.04) between the population sample and SARS-CoV-2-positive subjects. In agreement with previous studies, a nonsignificantly higher frequency of minor allele carriers was detected among hospitalized COVID-19 subjects. We conclude that a common polymorphism in the ABCA3 gene may be a significant predictor of susceptibility to SARS-CoV-2 infection.
- MeSH
- ABC transportéry genetika MeSH
- COVID-19 * diagnóza epidemiologie genetika MeSH
- genotyp MeSH
- lidé MeSH
- polymorfismus genetický MeSH
- SARS-CoV-2 MeSH
- transkripční faktory genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- ABC transportéry MeSH
- ABCA3 protein, human MeSH Prohlížeč
- LZTFL1 protein, human MeSH Prohlížeč
- transkripční faktory MeSH
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that spread around the world during the past 2 years, has infected more than 260 million people worldwide and has imposed an important burden on the healthcare system. Several risk factors associated with unfavorable outcome were identified, including elderly age, selected comorbidities, immune suppression as well as laboratory markers. The role of immune system in the pathophysiology of SARS-CoV-2 infection is indisputable: while an appropriate function of the immune system is important for a rapid clearance of the virus, progression to the severe and critical phases of the disease is related to an exaggerated immune response associated with a cytokine storm. We analyzed differences and longitudinal changes in selected immune parameters in 823 adult COVID-19 patients hospitalized in the Martin University Hospital, Martin, Slovakia. Examined parameters included the differential blood cell counts, various parameters of cellular and humoral immunity (serum concentration of immunoglobulins, C4 and C3), lymphocyte subsets (CD3+, CD4+, CD8+, CD19+, NK cells, CD4+CD45RO+), expression of activation (HLA-DR, CD38) and inhibition markers (CD159/NKG2A). Besides already known changes in the differential blood cell counts and basic lymphocyte subsets, we found significantly higher proportion of CD8+CD38+ cells and significantly lower proportion of CD8+NKG2A+ and NK NKG2A+ cells on admission in non-survivors, compared to survivors; recovery in survivors was associated with a significant increase in the expression of HLA-DR and with a significant decrease of the proportion of CD8+CD38+cells. Furthermore, patients with fatal outcome had significantly lower concentrations of C3 and IgM on admission. However, none of the examined parameters had sufficient sensitivity or specificity to be considered a biomarker of fatal outcome. Understanding the dynamic changes in immune profile of COVID-19 patients may help us to better understand the pathophysiology of the disease, potentially improve management of hospitalized patients and enable proper timing and selection of immunomodulator drugs.
- Klíčová slova
- COVID-19, SARS-CoV-2, activated CD8+ cells, clinical outcome, immune cell dysregulation, immunologic predictors,
- MeSH
- CD8-pozitivní T-lymfocyty * imunologie MeSH
- COVID-19 * diagnóza imunologie MeSH
- dospělí MeSH
- HLA-DR antigeny MeSH
- lidé MeSH
- podskupiny lymfocytů MeSH
- SARS-CoV-2 MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- HLA-DR antigeny MeSH