High-affinity FcγRIIIa genetic variants and potent NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) responses contributing to severe COVID-19

Vietzen, Hannes; Danklmaier, Vera; Zoufaly, Alexander; Puchhammer‐Stöckl, Elisabeth

doi:10.1016/j.gim.2022.04.005

Cited by 18 publications

(14 citation statements)

References 32 publications

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“…observed an expansion of the CD56 dim CD16 neg NK subset and lower cytotoxic capacities in COVID-19 patients (32). Our results agree with the reports stating that SARS-CoV-2specific NK cell-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) responses were subjected to NK cell FcγRIIIa genetic variants (33) and the normal activity of NK cells might improve the control of COVID-19 by fighting the virus and suppressing fibrosis progression (34,35). Briefly, NK cells exhibit anti-SARS-CoV-2 activity.…”

Section: Discussionsupporting

confidence: 92%

Redistribution and activation of CD16^brightCD56^dimNK cell subset to fight against Omicron subvariant BA.2 after COVID-19 vaccination

Liu

Peng

Xiang

et al. 2023

Preprint

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With the alarming surge in COVID-19 cases globally, vaccination must be prioritised to achieve herd immunity. Immune dysfunction is detected in the majority of patients with COVID-19; however, it remains unclear whether the immune responses elicited by COVID-19 vaccination function against the Omicron subvariant BA.2. Of the 508 Omicron BA.2-infected patients enrolled, 102 were unvaccinated controls and 406 were vaccinated. Despite the presence of clinical symptoms in both groups, vaccination led to a significant decline in nausea or vomiting, abdominal pain, headache, pulmonary infection, overall clinical symptoms, and a moderate rise in body temperature. Omicron BA.2-infected individuals were also characterised by a mild increase in both serum pro- and anti-inflammatory cytokine levels after vaccination. There were no significant differences or trend changes between T and B lymphocyte subsets; however, a significant expansion of NK lymphocytes in COVID-19-vaccinated patients was observed. Moreover, the most effective CD16brightCD56dimsubsets of NK cells showed increased functional capacities, as evidenced by a significantly greater IFN-γ secretion and stronger cytotoxic potential in Omicron BA.2-infected patients after vaccination. Collectively, these results suggest that COVID-19 vaccination interventions promote the redistribution and activation of CD16brightCD56dimNK cell subsets against viral infections, and could facilitate the clinical management of Omicron BA.2-infected patients.

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Section: Discussionsupporting

confidence: 92%

Redistribution and activation of CD16^brightCD56^dimNK cell subset to fight against Omicron subvariant BA.2 after COVID-19 vaccination

Liu

Peng

Xiang

et al. 2023

Preprint

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“…Between 30% and 50% of all CD56 bright NK cells express the CD16a/FcγRIIIa‐receptor 6 and we recently identified the high‐affinity FCGR3A ‐158‐V/V genotype as a risk factor for severe COVID‐19. 19 In the present study, we could confirm this finding. In addition, we were also able to further specify that the FCGR3A ‐158‐V/V variant was highly associated with an increased risk for a fatal disease only in younger COVID‐19 patients and especially in individuals, who also encoded for the rs9916629 ‐ C allele.…”

Section: Discussionsupporting

confidence: 79%

The natural killer cell‐associated rs9916629‐C allele is a novel genetic risk factor for fatal COVID‐19

Vietzen

Furlano

Traugott³

et al. 2022

Journal of Medical Virology

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The severity of COVID‐19 is associated with individual genetic host factors. Among these, genetic polymorphisms affecting natural killer (NK) cell responses, as variations in the HLA‐E‐ (HLA‐E*0101/0103), FcγRIIIa‐ (FcγRIIIa‐158‐F/V), and NKG2C‐ (KLRC2wt/del) receptor, were associated with severe COVID‐19. Recently, the rs9916629‐C/T genetic polymorphism was identified that indirectly shape the human NK cell repertoire towards highly pro‐inflammatory CD56bright NK cells. We investigated whether the rs9916629‐C/T variants alone and in comparison to the other risk factors are associated with a fatal course of COVID‐19. We included 1042 hospitalized surviving and 159 nonsurviving COVID‐19 patients as well as 1000 healthy controls. rs9916629‐C/T variants were genotyped by TaqMan assays and were compared between the groups. The patients' age, comorbidities, HLA‐E*0101/0103, FcγRIIIa‐158‐F/V, and KLRC2wt/del variants were also determined. The presence of the rs9916629‐C allele was a risk factor for severe and fatal COVID‐19 (p < 0.0001), independent of the patients' age or comorbidities. Fatal COVID‐19 was more frequent in younger patients (<69.85 years) carrying the FcγRIIIa‐158‐V/V (p < 0.006) and in older patients expressing the KLRC2del variant (p < 0.003). Thus, patients with the rs9916629‐C allele have a significantly increased risk for fatal COVID‐19 and identification of the genetic variants may be used as prognostic marker for hospitalized COVID‐19 patients.

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“…Specific subtypes of CD4+ T cells, such as Th and Tfh cells, could stimulate B cell differentiation and antibody production by secreting cytokines and chemokines 43 . On the other hand, antibodies could mediate antibody‐dependent cytotoxicity (ADCC) through NK cells, exacerbating disease severity 44 . Older adults, males, underlying diseases (hypertension, endocrine diseases), and immune‐suppression states (glucocorticoid and immunoglobulin therapy) served as high‐risk factors, which may be caused by the increased risk of coagulation disorders 4,45 and dysregulated immune response 46,47 in patients under such immune status.…”

Section: Discussionmentioning

confidence: 99%

“…Cervia et al 40 43 On the other hand, antibodies could mediate antibody-dependent cytotoxicity (ADCC) through NK cells, exacerbating disease severity. 44 Older adults, males, underlying diseases (hypertension, endocrine diseases), and immune-suppression states (glucocorticoid and immunoglobulin therapy) served as high-risk factors, which may be caused by the increased risk of coagulation disorders 4,45 and dysregulated immune response 46,47 in patients under such immune status. Overall, the highest weighting of these metrics in this newly established novel LTAP model supported the observation of elevated IgG levels in patients with higher disease severity.…”

Section: Comparison Of Our Ltap Model Against Other Methods For the S...mentioning

confidence: 99%

Long‐term SARS‐CoV‐2 neutralizing antibody level prediction using multimodal deep learning: A prospective cohort study on longitudinal data in Wuhan, China

Fang,

Yan,

Chen

et al. 2023

Journal of Medical Virology

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The ongoing epidemic of SARS‐CoV‐2 is taking a substantial financial and health toll on people worldwide. Assessing the level and duration of SARS‐CoV‐2 neutralizing antibody (Nab) would provide key information for government to make sound healthcare policies. Assessed at 3‐, 6‐, 12‐, and 18‐month postdischarge, we described the temporal change of IgG levels in 450 individuals with moderate to critical COVID‐19 infection. Moreover, a data imputation framework combined with a novel deep learning model was implemented to predict the long‐term Nab and IgG levels in these patients. Demographic characteristics, inspection reports, and CT scans during hospitalization were used in this model. Interpretability of the model was further validated with Shapely Additive exPlanation (SHAP) and Gradient‐weighted Class Activation Mapping (GradCAM). IgG levels peaked at 3 months and remained stable in 12 months postdischarge, followed by a significant decline in 18 months postdischarge. However, the Nab levels declined from 6 months postdischarge. By training on the cohort of 450 patients, our long‐term antibody prediction (LTAP) model could predict long‐term IgG levels with relatively high area under the receiver operating characteristic curve (AUC), accuracy, precision, recall, and F1‐score, which far exceeds the performance achievable by commonly used models. Several prognostic factors including FDP levels, the percentages of T cells, B cells and natural killer cells, older age, sex, underlying diseases, and so forth, served as important indicators for IgG prediction. Based on these top 15 prognostic factors identified in IgG prediction, a simplified LTAP model for Nab level prediction was established and achieved an AUC of 0.828, which was 8.9% higher than MLP and 6.6% higher than LSTM. The close correlation between IgG and Nab levels making it possible to predict long‐term Nab levels based on the factors selected by our LTAP model. Furthermore, our model identified that coagulation disorders and excessive immune response, which indicate disease severity, are closely related to the production of IgG and Nab. This universal model can be used as routine discharge tests to identify virus‐infected individuals at risk for recurrent infection and determine the optimal timing of vaccination for general populations.

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High-affinity FcγRIIIa genetic variants and potent NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) responses contributing to severe COVID-19

Cited by 18 publications

References 32 publications

Redistribution and activation of CD16^brightCD56^dimNK cell subset to fight against Omicron subvariant BA.2 after COVID-19 vaccination

Redistribution and activation of CD16^brightCD56^dimNK cell subset to fight against Omicron subvariant BA.2 after COVID-19 vaccination

The natural killer cell‐associated rs9916629‐C allele is a novel genetic risk factor for fatal COVID‐19

Long‐term SARS‐CoV‐2 neutralizing antibody level prediction using multimodal deep learning: A prospective cohort study on longitudinal data in Wuhan, China

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High-affinity FcγRIIIa genetic variants and potent NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) responses contributing to severe COVID-19

Cited by 18 publications

References 32 publications

Redistribution and activation of CD16brightCD56dimNK cell subset to fight against Omicron subvariant BA.2 after COVID-19 vaccination

Redistribution and activation of CD16brightCD56dimNK cell subset to fight against Omicron subvariant BA.2 after COVID-19 vaccination

The natural killer cell‐associated rs9916629‐C allele is a novel genetic risk factor for fatal COVID‐19

Long‐term SARS‐CoV‐2 neutralizing antibody level prediction using multimodal deep learning: A prospective cohort study on longitudinal data in Wuhan, China

Contact Info

Product

Resources

About

Redistribution and activation of CD16^brightCD56^dimNK cell subset to fight against Omicron subvariant BA.2 after COVID-19 vaccination

Redistribution and activation of CD16^brightCD56^dimNK cell subset to fight against Omicron subvariant BA.2 after COVID-19 vaccination