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      Long-COVID post-viral chronic fatigue and affective symptoms are associated with oxidative damage, lowered antioxidant defenses and inflammation: a proof of concept and mechanism study

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          Abstract

          The immune-inflammatory response during the acute phase of COVID-19, as assessed using peak body temperature (PBT) and peripheral oxygen saturation (SpO2), predicts the severity of chronic fatigue, depression and anxiety symptoms 3–4 months later. The present study was performed to examine the effects of SpO2 and PBT during acute infection on immune, oxidative and nitrosative stress (IO&NS) pathways and neuropsychiatric symptoms of Long COVID. This study assayed SpO2 and PBT during acute COVID-19, and C-reactive protein (CRP), malondialdehyde (MDA), protein carbonyls (PCs), myeloperoxidase (MPO), nitric oxide (NO), zinc, and glutathione peroxidase (Gpx) in 120 Long COVID individuals and 36 controls. Cluster analysis showed that 31.7% of the Long COVID patients had severe abnormalities in SpO2, body temperature, increased oxidative toxicity (OSTOX) and lowered antioxidant defenses (ANTIOX), and increased total Hamilton Depression (HAMD) and Anxiety (HAMA) and Fibromylagia-Fatigue (FF) scores. Around 60% of the variance in the neuropsychiatric symptoms of Long COVID (a factor extracted from HAMD, HAMA and FF scores) was explained by OSTOX/ANTIOX ratio, PBT and SpO2. Increased PBT predicted increased CRP and lowered ANTIOX and zinc levels, while lowered SpO2 predicted lowered Gpx and increased NO production. Lowered SpO2 strongly predicts OSTOX/ANTIOX during Long COVID. In conclusion, the impact of acute COVID-19 on the symptoms of Long COVID is partly mediated by OSTOX/ANTIOX, especially lowered Gpx and zinc, increased MPO and NO production and lipid peroxidation-associated aldehyde formation. The results suggest that post-viral somatic and mental symptoms have a neuroimmune and neuro-oxidative origin.

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          Most cited references121

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

            Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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              Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China

              Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. Risk factors for the clinical outcomes of COVID-19 pneumonia have not yet been well delineated.
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                Author and article information

                Contributors
                dr.michaelmaes@hotmail.com
                Journal
                Mol Psychiatry
                Mol Psychiatry
                Molecular Psychiatry
                Nature Publishing Group UK (London )
                1359-4184
                1476-5578
                24 October 2022
                : 1-15
                Affiliations
                [1 ]GRID grid.442852.d, ISNI 0000 0000 9836 5198, Department of Chemistry, College of Science, , University of Kufa, ; Kufa, Iraq
                [2 ]GRID grid.513683.a, ISNI 0000 0004 8495 7394, College of Medical laboratory Techniques, , Imam Ja’afar Al-Sadiq University, ; Najaf, Iraq
                [3 ]Al-Najaf Center for Cardiac Surgery and Transcatheter Therapy, Najaf, Iraq
                [4 ]GRID grid.444971.b, ISNI 0000 0004 6023 831X, Medical Laboratory Technology Department, College of Medical Technology, , The Islamic University, ; Najaf, Iraq
                [5 ]GRID grid.7922.e, ISNI 0000 0001 0244 7875, Department of Psychiatry, Faculty of Medicine, , Chulalongkorn University, ; Bangkok, Thailand
                [6 ]GRID grid.35371.33, ISNI 0000 0001 0726 0380, Department of Psychiatry, , Medical University of Plovdiv, ; Plovdiv, Bulgaria
                [7 ]GRID grid.414257.1, ISNI 0000 0004 0540 0062, Deakin University, IMPACT, the Institute for Mental and Physical Health and Clinical Translation, , School of Medicine, Barwon Health, ; Geelong, VIC Australia
                Author information
                http://orcid.org/0000-0001-6143-5196
                http://orcid.org/0000-0002-7667-6731
                http://orcid.org/0000-0002-2012-871X
                Article
                1836
                10.1038/s41380-022-01836-9
                9589528
                36280755
                b1ff740a-9979-4bb6-a02e-ed41b985c8d3
                © The Author(s), under exclusive licence to Springer Nature Limited 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 30 April 2022
                : 1 October 2022
                : 10 October 2022
                Funding
                Funded by: Islamic University of Najaf
                Categories
                Article

                Molecular medicine
                molecular biology,neuroscience
                Molecular medicine
                molecular biology, neuroscience

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