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      Secondary infections and long-term outcomes among hospitalized elderly and non-elderly patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and treated with baricitinib: a comparative study from the national centre of Hungary

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          Abstract

          Baricitinib is considered a first-line treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected adult patients with an associated cytokine storm syndrome (CSS). Our objective was to compare rates of secondary infections and long-term outcomes of elderly and non-elderly patients who received baricitinib for COVID-19. We conducted a single-centre observational study between November 2020 and September 2023, focusing on hospitalized adult SARS-CoV-2 patients with CSS, categorized as elderly (≥ 65 years) and non-elderly (< 65 years). Enrolment, severity stratification, and diagnosis of infectious complications followed predefined criteria. Outcomes of all-cause mortality and rates of non-severe and severe secondary infections were assessed at 1-year post-treatment initiation. Kaplan–Meier analysis was performed for survival analysis. In total, 490 patients were enrolled (median age 65 ± 23 (21–100) years (years, median ± IQR, min–max); 49.18% elderly; 59.59% male). Elderly patients were admitted to the hospital significantly earlier (7 ± 5 days vs. 8 ± 4 days; p = 0.02), experienced a higher occurrence of severe COVID-19 (121/241, 50.21% vs. 98/249, 39.36%; p = 0.02), and required the use of non-invasive ventilation at baseline (167/225, 74.22% vs. 153/236, 64.83%; p = 0.03). At 1 year, all-cause mortality was significantly higher in the elderly subgroup (111/241, 46.06% vs. 29/249, 11.65%; p < 0.01). At 90 days and 1 year, rates of any severe secondary infection were also more prevalent among the elderly (56/241, 23.24% vs. 37/249 14.86%; p = 0.02 and 58/241, 24.07% vs. 39/249, 15.66%; p = 0.02). In conclusion, elderly SARS-CoV-2-infected patients experience a more severe clinical course, higher secondary infection rates, and increased risk for long-term mortality, regardless of immunomodulatory therapy.

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          Baricitinib: A Review in Rheumatoid Arthritis

          Baricitinib (Olumiant®) is an oral, targeted synthetic DMARD that inhibits JAK1 and JAK2, which are implicated in the pathogenesis of rheumatoid arthritis (RA). This novel, small molecule is approved for use as monotherapy, or in combination with methotrexate, for the treatment of adults with moderate to severe active RA who responded inadequately to or were intolerant of ≥ 1 DMARD. In pivotal multinational trials, once-daily baricitinib 4 mg, with/without methotrexate (± another csDMARD), improved the signs and symptoms of RA, disease activity and physical function in DMARD-naive patients and in patients with an inadequate response to methotrexate, csDMARDs or TNF inhibitors; baricitinib treatment also slowed structural joint damage in DMARD-naive patients and in those with an inadequate response to methotrexate and csDMARDs. Baricitinib plus methotrexate was more effective than adalimumab plus methotrexate in patients with an inadequate response to methotrexate. The onset of these benefits was generally rapid and sustained over time. Baricitinib was generally well tolerated during up to 5.5 years' treatment; the most commonly reported adverse drug reactions were upper respiratory tract infections, increased LDL cholesterol, nausea and thrombocytosis. Thus, once-daily baricitinib, as monotherapy or in combination with methotrexate, is an effective and generally well tolerated emerging treatment for patients with moderate to severe active RA who have responded inadequately to or are intolerant of ≥ 1 DMARD, and extends the options available for this population.
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            COVID-19 and cellular senescence

            The clinical severity of coronavirus disease 2019 (COVID-19) is largely determined by host factors. Recent advances point to cellular senescence, an ageing-related switch in cellular state, as a critical regulator of SARS-CoV-2-evoked hyperinflammation. SARS-CoV-2, like other viruses, can induce senescence and exacerbates the senescence-associated secretory phenotype (SASP), which is comprised largely of pro-inflammatory, extracellular matrix-degrading, complement-activating and pro-coagulatory factors secreted by senescent cells. These effects are enhanced in elderly individuals who have an increased proportion of pre-existing senescent cells in their tissues. SASP factors can contribute to a ‘cytokine storm’, tissue-destructive immune cell infiltration, endothelialitis (endotheliitis), fibrosis and microthrombosis. SASP-driven spreading of cellular senescence uncouples tissue injury from direct SARS-CoV-2-inflicted cellular damage in a paracrine fashion and can further amplify the SASP by increasing the burden of senescent cells. Preclinical and early clinical studies indicate that targeted elimination of senescent cells may offer a novel therapeutic opportunity to attenuate clinical deterioration in COVID-19 and improve resilience following infection with SARS-CoV-2 or other pathogens. Many viruses, including SARS-CoV-2, can induce cellular senescence and exacerbate the senescence-associated secretory phenotype, leading to detrimental hyperinflammatory responses. Here, Schmitt and colleagues discuss the role of cellular senescence in COVID-19 as well as progress in the development of therapeutic approaches to eliminate senescent cells.
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              Nursing homes and the elderly regarding the COVID-19 pandemic: situation report from Hungary

              The global impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is significant in terms of public health effects and its long-term socio-economic implications. Among all social groups, the elderly is by far the most affected age group regarding morbidity and mortality. In multiple countries spanning several continents, there are an increasing number of reports referencing the novel coronavirus disease-2019 (COVID-19) spread among nursing homes. These areas are now recognized as potent hotspots regarding the pandemic, which one considers with special regard. Herein, we present currently available data of fatal COVID-19 cases throughout Hungary, along with the analysis of the co-morbidity network. We also report on viral genomic data originating from a nursing home resident. The genomic data was used for viral haplotype network analysis. We emphasize the urgent need for public health authorities to focus on nursing homes and residential service units worldwide, especially in the care of the elderly and infirmed. Our results further emphasize the recent statement released by the World Health Organization (WHO) regarding the vulnerability among seniors and especially the high risk of COVID-19 emergence throughout nursing and social homes.
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                Author and article information

                Contributors
                szabo.balint.gergely@gmail.com
                Journal
                GeroScience
                Geroscience
                GeroScience
                Springer International Publishing (Cham )
                2509-2715
                2509-2723
                17 February 2024
                17 February 2024
                June 2024
                : 46
                : 3
                : 2863-2877
                Affiliations
                [1 ]National Institute of Haematology and Infectious Diseases, Central Hospital of Southern Pest, Albert Flórián Street 5-7., 1097 Budapest, Hungary
                [2 ]School of PhD Studies, Semmelweis University, ( https://ror.org/01g9ty582) Üllői Street 26., 1085 Budapest, Hungary
                [3 ]Departmental Group of Infectious Diseases, Department of Internal Medicine and Haematology, Semmelweis University, ( https://ror.org/01g9ty582) Üllői Street 26., 1085 Budapest, Hungary
                [4 ]Laboratory of Molecular Genetics, National Institute of Haematology and Infectious Diseases, Central Hospital of Southern Pest, Albert Flórián Street 5-7., 1097 Budapest, Hungary
                [5 ]Faculty of Medicine, Semmelweis University, ( https://ror.org/01g9ty582) Üllői Street 26., 1085 Budapest, Hungary
                [6 ]Department of Transfusion Medicine, Semmelweis University, ( https://ror.org/01g9ty582) Üllői Street 26., 1085 Budapest, Hungary
                Author information
                http://orcid.org/0000-0003-1775-1356
                Article
                1099
                10.1007/s11357-024-01099-y
                11009165
                38367195
                c51ec50f-8d69-44ad-a490-0accd1709181
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 10 September 2023
                : 3 February 2024
                Funding
                Funded by: Semmelweis University
                Categories
                Original Article
                Custom metadata
                © American Aging Association 2024

                coronavirus disease 2019,severe acute respiratory syndrome coronavirus 2,covid-19,sars-cov-2,immunomodulation,baricitinib,elderly,secondary infection

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