Upregulation of FOXP3 is associated with severity of hypoxia and poor outcomes in COVID-19 patients

Abdelhafiz, Ahmed Samir; Fouad, Mahmoud; Sayed‐Ahmed, Mohamed M.; Kamel, Mahmoud M.; Ali, Asmaa; Fouda, Merhan A.; Khalil, Mahmoud A F; Abdel‐Moneim, Ahmed S.; Kamal, Lamyaa Mohamed

doi:10.1016/j.virol.2021.08.012

Cited by 12 publications

(10 citation statements)

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“…COVID-19 is associated with immune dysregulation, which is related to the severity of the disease [ 27 ]. Restoration of baseline and homeostasis after COVID-19 needs some time, which is expected to be longer in severe forms of the diseases.…”

Section: Discussionmentioning

confidence: 99%

Predictors of post-COVID symptoms in Egyptian patients: Drugs used in COVID-19 treatment are incriminated

et al. 2022

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Objectives COVID-19 is a multisystem disease, and some patients suffer from physical or psychological symptoms for weeks or even months after infection, which is described as post-COVID syndrome. The goal of this study is evaluating the prevalence of post-COVID-19 symptoms among Egyptian patients and detecting the factors associated with the presence of these symptoms. Methods An on-line cross-sectional survey using Google Forms was used to conduct the present study, which took place between June and August 2021. Results Three hundred and ninety-six participants filled in the survey. The mean age of participants was 41.4 years. Most participants had mild to moderate COVID-19 (81.31%). The prevalence of post-COVID-19 symptoms was 87.63%, where the most frequent symptom was fatigue (60.86%). Female sex, the presence of comorbidities, lower degree of education, longer disease duration, as well as severe and critical forms of the disease were significantly associated with the presence of post-COVID symptoms. Using regression analysis, the predictors of post-COVID symptoms were severe and critical forms of the disease and intake of antibiotics and corticosteroids for treatment of COVID-19. Conclusions COVID-19 is followed by high prevalence of post-COVID symptoms. To the best of our knowledge, this is the first study to report the relationship between the use of antibiotics and the development of post-COVID symptoms. We recommend further studies to understand this relationship. We also recommend restricting the use of these drugs to indicated cases according to the international guidelines. More studies are needed to gain better understanding of post-COVID symptoms especially in females.

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Section: Discussionmentioning

confidence: 99%

Predictors of post-COVID symptoms in Egyptian patients: Drugs used in COVID-19 treatment are incriminated

et al. 2022

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“…In contrast to the present study's findings, Abdelhafiz et al discovered a significant decrease in FOXP3 in COVID-19 patients, suggesting that immunological dysregulation in COVID-19 patients is one of the consequences of this shift. Abdelhafiz et al also discovered that FOXP3 is a favorable predictive factor in individuals with severe symptoms and is elevated in these patients, resulting in hypoxia, which can lead to ARDS (30). In a study by Rezaei et al, no significant changes were observed in the FOXP3 expression level throughout the first week of the sickness.…”

Section: Discussionmentioning

confidence: 97%

Immunologic Profile of Severe COVID-19 Patients in Alborz Province, Iran

Shafiee

Rezaian

Aliyu

et al. 2023

Jundishapur J Microbiol

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Background: The coronavirus disease 2019 (COVID-19) pandemic has prompted researchers to look for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenicity in depth. Immune system dysregulation was one of the major mechanisms in its pathogenesis. The evidence regarding the levels of interferons (IFNs) and pro- and anti-inflammatory cytokines in COVID-19 patients is not well-established. Objectives: Therefore, this study evaluated the expression level of type-I, II, III IFNs, along with interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10), and FOXP3 genes in patients with severe COVID-19 to provide additional insights regarding the regulation of these cytokines during COVID-19 infection. Methods: Peripheral blood mononuclear cells were isolated from two groups, including severe COVID-19 patients and healthy controls. Ribonucleic acid was extracted to evaluate the expression level of IFN-a, IFN-b, IFN-g, IFN-la, IL-1, IL-6, IL-10, and FOXP3 genes using real-time polymerase chain reaction. The correlations between the expression levels of these genes were also assessed. Results: A total of 40 samples were divided into two groups, with each group consisting of 20 samples. When comparing the severe COVID-19 group to the controls, the expression levels of IFN-g, tumor necrosis factor-alpha (TNF-α), IL-6, and IL-10 genes were significantly higher in the severe COVID-19 group. The two groups had no significant differences in IFN-a, IFN-b, IFN-la, IL-1, and FOXP3 expression. The correlation analysis revealed a negative correlation between type I and type III IFNs (i.e., IFN-a and IFN-la) and pro-inflammatory cytokines (i.e., IL-1 and IL-10). Conclusions: This study suggests the possible upregulation of IFN-g, IL-6, IL-10, and TNF-α during SARS-CoV-2 pathogenicity. The preliminary findings of this study and those reported previously show that the levels of IFNs and pro- and anti-inflammatory cytokines are not uniformly expressed among all COVID-19 patients and might differ as the disease progresses to the severe stage.

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“…Interestingly, FoxP3, which improves the expansion of Treg cells’ function is severely downregulated in SARS-CoV-2 infection and coincides with COVID-19 severity [ 88 ]. Mohebbi et al study revealed that FoxP3 might be a potential biomarker for the assessment of COVID-19 severity [ 89 ].…”

Section: Role Of Neuropilin-1 In Covid-19mentioning

confidence: 99%

Role of Neuropilin 1 in COVID-19 Patients with Acute Ischemic Stroke

et al. 2022

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Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection can trigger the adaptive and innate immune responses, leading to uncontrolled inflammatory reactions and associated local and systematic tissue damage, along with thromboembolic disorders that may increase the risk of acute ischemic stroke (AIS) in COVID-19 patients. The neuropilin (NRP-1) which is a co-receptor for the vascular endothelial growth factor (VEGF), integrins, and plexins, is involved in the pathogenesis of AIS. NRP-1 is also regarded as a co-receptor for the entry of SARS-CoV-2 and facilitates its entry into the brain through the olfactory epithelium. NRP-1 is regarded as a cofactor for binding of SARS-CoV-2 with angiotensin-converting enzyme 2 (ACE2), since the absence of ACE2 reduces SARS-CoV-2 infectivity even in presence of NRP-1. Therefore, the aim of the present study was to clarify the potential role of NRP-1 in COVID-19 patients with AIS. SARS-CoV-2 may transmit to the brain through NRP-1 in the olfactory epithelium of the nasal cavity, leading to different neurological disorders, and therefore about 45% of COVID-19 patients had neurological manifestations. NRP-1 has the potential capability to attenuate neuroinflammation, blood–brain barrier (BBB) permeability, cerebral endothelial dysfunction (ED), and neuronal dysfunction that are uncommon in COVID-19 with neurological involvement, including AIS. Similarly, high NRP-1 serum level is linked with ED, oxidative stress, and the risk of pulmonary thrombosis in patients with severe COVID-19, suggesting a compensatory mechanism to overcome immuno-inflammatory disorders. In conclusion, NRP-1 has an important role in the pathogenesis of COVID-19 and AIS, and could be the potential biomarker linking the development of AIS in COVID-19. The present findings cannot provide a final conclusion, and thus in silico, experimental, in vitro, in vivo, preclinical, and clinical studies are recommended to confirm the potential role of NRP-1 in COVID-19, and to elucidate the pharmacological role of NRP-1 receptor agonists and antagonists in COVID-19.

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Upregulation of FOXP3 is associated with severity of hypoxia and poor outcomes in COVID-19 patients

Cited by 12 publications

References 54 publications

Predictors of post-COVID symptoms in Egyptian patients: Drugs used in COVID-19 treatment are incriminated

Predictors of post-COVID symptoms in Egyptian patients: Drugs used in COVID-19 treatment are incriminated

Immunologic Profile of Severe COVID-19 Patients in Alborz Province, Iran

Role of Neuropilin 1 in COVID-19 Patients with Acute Ischemic Stroke

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