Immunogenetic Predictors of Severe COVID-19

Малкова, Анна; Kudlаy, D.А.; Kudryavtsev, I. V.; Старшинова, Анна; Yablonskiy, Piotr; Shoenfeld, Yehuda

doi:10.3390/vaccines9030211

Cited by 48 publications

(42 citation statements)

References 66 publications

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“…It was previously reported that patients with severe COVID-19 showed higher leukocyte and neutrophil counts, a higher neutrophil-to-lymphocyte ratio (NLR), and lower levels of monocytes, eosinophils, and basophils compared to those in patients with moderate disease severity [ 3 , 5 , 7 , 30 , 31 , 32 ]. In addition, a higher neutrophil count and NLR were associated with the severity of infection [ 30 ] and could be predictors of a poor prognosis [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

“…In most cases, lymphopenia with decreased absolute counts of CD4+ and CD8+ T cells, B cells, and natural killers (NK) cells have been detected in patients with COVID-19, excluding mild forms [ 3 , 4 , 5 , 6 , 7 ]. Decreased levels of total T cells as well as CD3+CD4+ and CD3+CD8+ subsets were primarily observed in elderly patients and were associated with infection severity and with the need for intensive care unit hospitalization [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Imbalanced Immune Response of T-Cell and B-Cell Subsets in Patients with Moderate and Severe COVID-19

Головкин

Kalinina

Bezrukikh

et al. 2021

Viruses

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Background: The immunological changes associated with COVID-19 are largely unknown. Methods: Patients with COVID-19 showing moderate (n = 18; SpO2 > 93%, respiratory rate > 22 per minute, CRP > 10 mg/L) and severe (n = 23; SpO2 < 93%, respiratory rate >30 per minute, PaO2/FiO2 ≤ 300 mmHg, permanent oxygen therapy, qSOFA > 2) infection, and 37 healthy donors (HD) were enrolled. Circulating T- and B-cell subsets were analyzed by flow cytometry. Results: CD4+Th cells were skewed toward Th2-like phenotypes within CD45RA+CD62L− (CM) and CD45RA–CD62L− (EM) cells in patients with severe COVID-19, while CM CCR6+ Th17-like cells were decreased if compared with HD. Within CM Th17-like cells “classical” Th17-like cells were increased and Th17.1-like cells were decreased in severe COVID-19 cases. Circulating CM follicular Th-like (Tfh) cells were decreased in all COVID-19 patients, and Tfh17-like cells represented the most predominant subset in severe COVID-19 cases. Both groups of patients showed increased levels of IgD-CD38++ B cells, while the levels of IgD+CD38− and IgD–CD38− were decreased. The frequency of IgD+CD27+ and IgD–CD27+ B cells was significantly reduced in severe COVID-19 cases. Conclusions: We showed an imbalance within almost all circulating memory Th subsets during acute COVID-19 and showed that altered Tfh polarization led to a dysregulated humoral immune response.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Imbalanced Immune Response of T-Cell and B-Cell Subsets in Patients with Moderate and Severe COVID-19

Головкин

Kalinina

Bezrukikh

et al. 2021

Viruses

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“…ERAP2 and its homolog ERAP1 constituted an efficient filter to epitope presentation by greatly limiting the diversity of virus antigenic peptides sequences produced, suggesting the promising value of ERAP2 in SARS-CoV-2 immunogenicity studies and vaccine design (41). The rs150892504 mutations in the ERAP2 gene were believed to be a genetic factor related to severe life-threatening complications in individuals infected with coronavirus (42). Since ERAP2 was involved in the renin-angiotensin system (RAS), ERAP2 dysfunction was hypothesized to exacerbate the symptomatology and prognosis of the SARS-CoV-2.…”

Section: Discussionmentioning

confidence: 99%

ERAP2 Is Associated With Immune Infiltration and Predicts Favorable Prognosis in SqCLC

et al. 2021

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BackgroundImmunotherapy has been proven effective among several human cancer types, including Squamous cell lung carcinoma (SqCLC). ERAP2 plays a pivotal role in peptide trimming of many immunological processes. However, the prognostic role of ERAP2 and its relationship with immune cell infiltration in SqCLC remains unclear.MethodsThe differential expression of ERAP2 was identified via GEO and TCGA databases. We calculated the impact of ERAP2 on clinical prognosis using the Kaplan-Meier plotter. TIMER was applied to evaluate the abundance of immune cells infiltration and immune markers. SqCLC tissue microarrays containing 190 patients were constructed, and we performed immunohistochemical staining for ERAP2, CD8, CD47, CD68, and PD-L1 to validate our findings in public data.ResultsIn the GEO SqCLC database, ERAP2 was upregulated in patients with better survival (p=0.001). ERAP2 expression in SqCLC was significantly lower than that of matched normal samples (p<0.05) based on TCGA SqCLC data. Higher expression of ERAP2 was significantly associated with better survival in SqCLC patients from TCGA (p=0.007), KM-plotter (p=0.017), and our tissue microarrays (TMAs) (p=0.026). In univariate and multivariate Cox analysis of SqCLC TMAs, high ERAP2 expression was identified as an independent protective factor for SqCLC patients (Univariate Cox, HR=0.659, range 0.454-0.956, p<0.05. Multivariate Cox, HR=0.578, range 0.385-0.866, p<0.05). In TIMER, ERAP2 was positively correlated with several immune markers (CD274, p=1.27E-04; CD68, p=5.88E-08) and immune infiltrating cells (CD8+ T cell, p=4.09E-03; NK cell, p=1.00E-04). In our cohort, ERAP2 was significantly correlated with CD8+ tumor-infiltrating lymphocytes (TILs) (p=0.0029), and patients with higher ERAP2 expression had a higher percentage of PD-L1 positive patients (p=0.049) and a higher CD8+ TILs level (p=0.036).ConclusionsFor the first time, our study demonstrates that higher expression of ERAP2 is tightly associated with the immuno-supportive microenvironment and can predict a favorable prognosis in SqCLC. Meanwhile, ERAP2 may be a promising immunotherapeutic target for patients with SqCLC.

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“…An important feature in the development of PCS after the asymptomatic/mild form is the predominance of female patients [14,20,68]. It is known that the female gender is a protective factor against the development of severe infections [69]. This is facilitated by several physiological characteristics, in particular:…”

Section: The Hypothesismentioning

confidence: 99%

Post COVID-19 Syndrome in Patients with Asymptomatic/Mild Form

et al. 2021

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Post COVID-19 Syndrome (PCS) is a complex of various symptoms developing a month or more after the acute phase of the disease. The cases of PCS development among patients with asymptomatic/mild forms are frequently reported; however, the pathogenesis of PCS in this group of patients is still not completely clear. The publications about COVID-19 which were published in online databases from December 2019 to September 2021 are analyzed in this review. According to the analysis, PCS develops on average in 30–60% of patients, mainly among women. Fatigue, shortness of breath, cough, and anosmia were reported as the most common symptoms. The possible association between the described PCS symptoms and brain damage was revealed. We assume the possibility of an alternative course of COVID-19, which develops in genetically predisposed individuals with a stronger immune response, in which it predominantly affects the cells of the nervous system, possibly with the presence of an autoimmune component, which might have similarity with chronic fatigue syndrome or autoimmune disautonomia. Thus, the gender (female) and the presence of anosmia during an asymptomatic or mild course of the disease can be predictive factors for the development of PCS, which can be caused by autoimmune damage to neurons, glia, and cerebral vessels.

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Immunogenetic Predictors of Severe COVID-19

Cited by 48 publications

References 66 publications

Imbalanced Immune Response of T-Cell and B-Cell Subsets in Patients with Moderate and Severe COVID-19

Imbalanced Immune Response of T-Cell and B-Cell Subsets in Patients with Moderate and Severe COVID-19

ERAP2 Is Associated With Immune Infiltration and Predicts Favorable Prognosis in SqCLC

Post COVID-19 Syndrome in Patients with Asymptomatic/Mild Form

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