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      The bioenergetics of COVID-19 immunopathology and the therapeutic potential of biophysical radiances

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          Abstract

          In developing an effective clinical tool against COVID-19, we need to consider why SARS-CoV-2 infections develops along remarkably different trajectories: from completely asymptomatic to a severe course of disease. In this paper we hypothesize that the progressive exhaustion and loss of lymphocytes associated with severe stages of COVID-19 results from an intracellular energy deficit in an organism which has already been depleted by preexisting chronic diseases, acute psychological stress and the aging process. A bioenergetics view of COVID-19 immunopathology opens a new biophysical opportunity to enhance impaired immune function via proposed pathways of photomagnetic catalysis of ATP synthesis, regenerative photobiomodulation and the ultrasonic acceleration of cell restructuring. Moreover, we suggest that a coherent application of multiple biophysical radiances (coMra) may synergistically enhance energy-matter-information kinetics of basal self-regeneration of cells and thus improve immune function and accelerate recovery.

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          Highlights

          • •

            Bioenergetics offers a unifying framework of COVID-19 immunopathology.

          • •

            Functional reserve of immune cells depends on the kinetics of basal housekeeping.

          • •

            Various biophysical stimuli enhance the kinetics of cellular self-regeneration.

          • •

            A coherent application of multiple radiances has potential to treat COVID-19.

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          Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

          Fei Zhou, Ting Yu, Ronghui Du … (2020)
          Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
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            Dysregulation of immune response in patients with COVID-19 in Wuhan, China

            Chuan Qin, Luoqi Zhou, Ziwei Hu … (2020)
            Abstract Background In December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan and rapidly spread throughout China. Methods Demographic and clinical data of all confirmed cases with COVID-19 on admission at Tongji Hospital from January 10 to February 12, 2020, were collected and analyzed. The data of laboratory examinations, including peripheral lymphocyte subsets, were analyzed and compared between severe and non-severe patients. Results Of the 452 patients with COVID-19 recruited, 286 were diagnosed as severe infection. The median age was 58 years and 235 were male. The most common symptoms were fever, shortness of breath, expectoration, fatigue, dry cough and myalgia. Severe cases tend to have lower lymphocytes counts, higher leukocytes counts and neutrophil-lymphocyte-ratio (NLR), as well as lower percentages of monocytes, eosinophils, and basophils. Most of severe cases demonstrated elevated levels of infection-related biomarkers and inflammatory cytokines. The number of T cells significantly decreased, and more hampered in severe cases. Both helper T cells and suppressor T cells in patients with COVID-19 were below normal levels, and lower level of helper T cells in severe group. The percentage of naïve helper T cells increased and memory helper T cells decreased in severe cases. Patients with COVID-19 also have lower level of regulatory T cells, and more obviously damaged in severe cases. Conclusions The novel coronavirus might mainly act on lymphocytes, especially T lymphocytes. Surveillance of NLR and lymphocyte subsets is helpful in the early screening of critical illness, diagnosis and treatment of COVID-19.
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              Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19)

              Bo Diao, Chenhui Wang, Yingjun Tan … (2020)
              Background: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed great threat to human health. T cells play a critical role in antiviral immunity but their numbers and functional state in COVID-19 patients remain largely unclear. Methods: We retrospectively reviewed the counts of T cells and serum cytokine concentration from data of 522 patients with laboratory-confirmed COVID-19 and 40 healthy controls. In addition, the expression of T cell exhaustion markers were measured in 14 COVID-19 cases. Results: The number of total T cells, CD4+ and CD8+ T cells were dramatically reduced in COVID-19 patients, especially in patients requiring Intensive Care Unit (ICU) care. Counts of total T cells, CD8+ T cells or CD4+ T cells lower than 800, 300, or 400/μL, respectively, were negatively correlated with patient survival. T cell numbers were negatively correlated to serum IL-6, IL-10, and TNF-α concentration, with patients in the disease resolution period showing reduced IL-6, IL-10, and TNF-α concentrations and restored T cell counts. T cells from COVID-19 patients had significantly higher levels of the exhausted marker PD-1. Increasing PD-1 and Tim-3 expression on T cells was seen as patients progressed from prodromal to overtly symptomatic stages. Conclusions: T cell counts are reduced significantly in COVID-19 patients, and the surviving T cells appear functionally exhausted. Non-ICU patients with total T cells counts lower than 800/μL may still require urgent intervention, even in the immediate absence of more severe symptoms due to a high risk for further deterioration in condition.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Photochem Photobiol B
                Journal ID (iso-abbrev): J Photochem Photobiol B
                Title: Journal of Photochemistry and Photobiology. B, Biology
                Publisher: Published by Elsevier B.V.
                ISSN (Print): 1011-1344
                ISSN (Electronic): 1873-2682
                Publication date PMC-release: 12 November 2020
                Publication date (Electronic): 12 November 2020
                Electronic Location Identifier: 112083
                Affiliations
                [a ]Radiant Life Technologies, Ltd., SNP 19, Žiar nad Hronom 965 01, Slovak Republic.
                [b ]No affiliation, Russia
                [c ]Department of Microbiology and Virology, Department of Immunology and Allergology, Medical Institute, RUDN University, Moscow, Russia
                Author notes
                [* ]Corresponding author at: ul. Choros-Gurkina 36-14, Gorno-Altaisk, 649000, Russia.
                Article
                Publisher Item ID: S1011-1344(20)30533-9 Publisher ID: 112083
                DOI: 10.1016/j.jphotobiol.2020.112083
                PMC ID: 7659653
                SO-VID: 2a9e77c3-add4-4d15-9c3f-368ca9718bfd
                Copyright © © 2020 Published by Elsevier B.V.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 20 August 2020
                Date revision received : 15 October 2020
                Date accepted : 9 November 2020
                Categories
                Subject: Short Review

                Keywords: covid-19,bioenergetics,low level infrared laser,magnetic field,ultrasound,photobiomodulation,comra
                Data availability:
                Keywords: covid-19, bioenergetics, low level infrared laser, magnetic field, ultrasound, photobiomodulation, comra

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