Transcriptional Profiling of SARS-CoV-2-Infected Calu-3 Cells Reveals Immune-Related Signaling Pathways

Pereira, Eric Petterson Viana; da Silva Felipe, Stela Mirla; de Freitas, Raquel Martins; da Cruz Freire, José Ednésio; Oliveira, Antonio Edson Rocha; Canabrava, Natália; Soares, Paula Matias; van Tilburg, Mauricio Fraga; Guedes, Maria Izabel Florindo; Grueter, Chad Eric; Ceccatto, Vânia Marilande

doi:10.3390/pathogens12111373

Cited by 2 publications

(1 citation statement)

References 136 publications

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“…Analysis of transcriptomes from SARS-CoV-2-infected cells has revealed cellular responses related to IFN signaling, innate immunity, inflammation, and defense against the virus. These transcriptional changes, even though temporary, can help characterize the early stages of the cellular response to SARS-CoV-2 infection, providing insights into COVID-19 pathogenesis at the airway epithelium level, as well as revealing potential biomarkers and drug targets [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of Factors Associated with Mortality in the Elderly Population with SARS-CoV-2 Infection: Results from a Longitudinal Observational Study from Romania

Birlutiu,

Neamtu,

Birlutiu

2024

Pharmaceuticals

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The progression of SARS-CoV-2 infection has been linked to a hospitalization rate of 20%. The susceptibility of SARS-CoV-2 infection increases with age, resulting in severe and atypical clinical forms of the disease. The severity of SARS-CoV-2 infection in the elderly population can be attributed to several factors, including the overexpression of angiotensin-converting enzyme 2 (ACE2) receptors, immunosenescence, and alterations in the intestinal microbiota that facilitate the cytokine storm. In light of these observations, we conducted a retrospective analysis based on prospectively collected data between 23 December 2021 and 30 April 2022 (the fourth wave of SARS-CoV-2 infection). We analyzed patients aged over 60 years who were hospitalized in a county hospital in Romania. The primary objective of our study was to assess the risk factors for an unfavorable outcome, while the secondary objective was to assess the clinical and baseline characteristics of the enrolled patients. We included 287 cases with a complete electronic medical record from this available cohort of patients. We aimed to retrospectively evaluate a group of 127 patients that progressed, unfortunately, toward an unfavorable outcome versus 160 patients with a favorable outcome. We used the Combined Ordinal Scale of Severity that combines the WHO ordinal scale and the degrees of inflammation to assess the severity of the patients at the time of the initial assessment. The age group between 70 and 79 years had the highest percentage, accounting for 48.0%—61 patients, of the deceased patients. We noted statistically significant differences between groups related to other cardiovascular diseases, nutritional status, hematological diseases, other neurological/mental or digestive disorders, and other comorbidities. Regarding the nutritional status of the patients, there was a statistically significant unfavorable outcome for all the age groups and the patients with a BMI > 30 kg/m2, p = 0.004. The presence of these factors was associated with an unfavorable outcome. Our results indicate that with the presence of cough, there was a statistically significant favorable outcome in the age group over 80 years, p ≤ 0.049. In terms of the presence of dyspnea in all groups of patients, it was associated with an unfavorable outcome, p ≤ 0.001. In our study, we analyzed laboratory test results to assess the level of inflammation across various WHO categories, focusing on the outcome groups determined by the average values of specific biomarkers. Our findings show that, with the exception of IL-6, all other biomarkers tend to rise progressively with the severity of the disease. Moreover, these biomarkers are significantly higher in patients experiencing adverse outcomes. The differences among severity categories and the outcome group are highly significant (p-values < 0.001). CART algorithm revealed a specific cut-off point for the WHO ordinal scale of 4 to stand out as an important reference value for patients at a high risk of developing critical forms of COVID-19. The high death rate can be attributed to proinflammatory status, hormonal changes, nutritional and vitamin D deficiencies, comorbidities, and atypical clinical pictures.

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Section: Introductionmentioning

confidence: 99%

Identification of Factors Associated with Mortality in the Elderly Population with SARS-CoV-2 Infection: Results from a Longitudinal Observational Study from Romania

Birlutiu,

Neamtu,

Birlutiu

2024

Pharmaceuticals

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Discovery of a pan anti-SARS-CoV-2 monoclonal antibody with highly efficient infected cell killing capacity for novel immunotherapeutic approaches

Abba Moussa,

Vazquez,

Chable-Bessia

et al. 2024

Emerging Microbes & Infections

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Unlocking the potential of broadly reactive coronavirus monoclonal antibodies (mAbs) and their derivatives offers a transformative therapeutic avenue against severe COVID-19, especially crucial for safeguarding high-risk populations. Novel mAb-based immunotherapies may help address the reduced efficacy of current vaccines and neutralizing mAbs caused by the emergence of variants of concern (VOCs). Using phage display technology, we discovered a pan-SARS-CoV-2 mAb (C10) that targets a conserved region within the receptor-binding domain (RBD) of the virus. Noteworthy, C10 demonstrates exceptional efficacy in recognizing all assessed VOCs, including recent Omicron variants. While C10 lacks direct neutralization capacity, it efficiently binds to infected lung epithelial cells and induces their lysis via natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC). Building upon this pan-SARS-CoV-2 mAb, we engineered C10-based, Chimeric Antigen Receptor (CAR)-T cells endowed with efficient killing capacity against SARS-CoV-2-infected lung epithelial cells. Notably, NK and CAR-T-cell mediated killing of lung infected cells effectively reduces viral titers. These findings highlight the potential of non-neutralizing mAbs in providing immune protection against emerging infectious diseases. Our work reveals a pan-SARS-CoV-2 mAb effective in targeting infected cells and demonstrates the proof-of-concept for the potential application of CAR-T cell therapy in combating SARS-CoV-2 infections. Furthermore, it holds promise for the development of innovative antibody-based and cell-based therapeutic strategies against severe COVID-19 by expanding the array of therapeutic options available for high-risk populations. Trial registration:

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Transcriptional Profiling of SARS-CoV-2-Infected Calu-3 Cells Reveals Immune-Related Signaling Pathways

Cited by 2 publications

References 136 publications

Identification of Factors Associated with Mortality in the Elderly Population with SARS-CoV-2 Infection: Results from a Longitudinal Observational Study from Romania

Identification of Factors Associated with Mortality in the Elderly Population with SARS-CoV-2 Infection: Results from a Longitudinal Observational Study from Romania

Discovery of a pan anti-SARS-CoV-2 monoclonal antibody with highly efficient infected cell killing capacity for novel immunotherapeutic approaches

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