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The Role of Acidosis in the Pathogenesis of Severe Forms of COVID-19 / Y. D. Nechipurenko, D. A. Semyonov, I. A. Lavrinenko [et al.] // Biology-Basel. - 2021. - Vol. 10, Is. 9. - Ст. 852, DOI 10.3390/biology10090852. - Cited References:86. - This research was funded by the Presidium of the Russian Academy of Sciences for Molecular and Cellular Biology and the Program of Fundamental Research for State Academies for years 2013-2020, project no. 01201363818. . - ISSN 2079-7737

РУБ Biology
Рубрики:
RESPIRATORY-ACIDOSIS
   LACTATE
   COAGULATION
   GLYCOLYSIS
   SECRETION
Кл.слова (ненормированные):
SARS-CoV-2 -- COVID-19 -- acidosis -- hypoxia -- saturation -- Bohr effect -- lactate -- pH
Аннотация: Simple Summary Recently, several studies have shown that acidosis, which is increased acidity in the blood and other body tissues, is often associated with severe COVID-19. In this article, we look at the mechanisms and consequences of acidosis that can lead to an exacerbation of COVID-19. We want to draw the attention of readers to the threshold values of such disease characteristics as hypoxia and acidosis, which are associated with a sharp deterioration in the patient's condition. Hypoxia and acidosis mutually reinforce each other according to the principle of a vicious cycle (that is, they are involved in a system of positive feedbacks). Elevated blood lactate (lactic acid) levels are associated with poor clinical outcomes in COVID patients. As a practical recommendation, we propose to pay more attention to the prevention of acidosis, including in the early stages of the disease, when the adjustment of homeostasis requires less effort and is less risky. COVID-19 has specific characteristics that distinguish this disease from many other infections. We suggest that the pathogenesis of severe forms of COVID-19 can be associated with acidosis. This review article discusses several mechanisms potentially linking the damaging effects of COVID-19 with acidosis and shows the existence of a vicious cycle between the development of hypoxia and acidosis in COVID-19 patients. At the early stages of the disease, inflammation, difficulty in gas exchange in the lungs and thrombosis collectively contribute to the onset of acidosis. In accordance with the Verigo-Bohr effect, a decrease in blood pH leads to a decrease in oxygen saturation, which contributes to the exacerbation of acidosis and results in a deterioration of the patient's condition. A decrease in pH can also cause conformational changes in the S-protein of the virus and thus lead to a decrease in the affinity and avidity of protective antibodies. Hypoxia and acidosis lead to dysregulation of the immune system and multidirectional pro- and anti-inflammatory reactions, resulting in the development of a "cytokine storm". In this review, we highlight the potential importance of supporting normal blood pH as an approach to COVID-19 therapy.

WOS
Держатели документа:
Russian Acad Sci, Engelhardt Inst Mol Biol, Lab DNA Prot Recognit, Moscow 119991, Russia.
Voyno Yasenetsky Krasnoyarsk State Med Univ, Inst Mol Med & Pathobiochem, Krasnoyarsk 660022, Russia.
Russian Acad Sci, Inst Biophys, Siberian Branch, Krasnoyarsk 660036, Russia.
Voronezh State Univ, Fac Med & Biol, Dept Human & Anim Physiol, Voronezh 394018, Russia.
Moscow Inst Phys & Technol, Dept Biol & Med Phys, Dolgoprudnyi 141701, Russia.
Lomonosov Moscow State Univ, Fac Phys, Dept Biophys, Moscow 119991, Russia.
Russian Acad Sci, Lab Med Analyt Methods & Devices, Inst Analyt Instrumentat, St Petersburg 198095, Russia.
Sendai Viralyt LLC, Acton, MA USA.
Russian Acad Sci, Engelhardt Inst Mol Biol, Lab Cellular Bases Dev Malignant Dis, Moscow 119991, Russia.

Доп.точки доступа:
Nechipurenko, Yury D.; Semyonov, Denis A.; Lavrinenko, Igor A.; Lagutkin, Denis A.; Generalov, Evgenii A.; Zaitceva, Anna Y.; Matveeva, Olga, V; Yegorov, Yegor E.; Lagutkin, Denis; Presidium of the Russian Academy of Sciences for Molecular and Cellular Biology; Program of Fundamental Research for State Academies for years 2013-2020 [01201363818]

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The role of acidosis in the pathogenesis of severe forms of COVID-19 / Y. D. Nechipurenko, D. A. Semyonov, I. A. Lavrinenko [et al.] // Biology. - 2021. - Vol. 10, Is. 9. - Ст. 852, DOI 10.3390/biology10090852 . - ISSN 2079-7737
Кл.слова (ненормированные):
Acidosis -- Bohr effect -- COVID-19 -- Hypoxia -- Lactate -- PH -- SARS-CoV-2 -- Saturation
Аннотация: COVID-19 has specific characteristics that distinguish this disease from many other infec-tions. We suggest that the pathogenesis of severe forms of COVID-19 can be associated with acidosis. This review article discusses several mechanisms potentially linking the damaging effects of COVID-19 with acidosis and shows the existence of a vicious cycle between the development of hypoxia and acidosis in COVID-19 patients. At the early stages of the disease, inflammation, difficulty in gas exchange in the lungs and thrombosis collectively contribute to the onset of acidosis. In accordance with the Verigo-Bohr effect, a decrease in blood pH leads to a decrease in oxygen saturation, which contributes to the exacerbation of acidosis and results in a deterioration of the patient’s condition. A decrease in pH can also cause conformational changes in the S-protein of the virus and thus lead to a decrease in the affinity and avidity of protective antibodies. Hypoxia and acidosis lead to dysregu-lation of the immune system and multidirectional pro-and anti-inflammatory reactions, resulting in the development of a “cytokine storm”. In this review, we highlight the potential importance of supporting normal blood pH as an approach to COVID-19 therapy. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Scopus
Держатели документа:
Laboratory DNA-Protein Recognition, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russian Federation
Institute of Molecular Medicine and Pathobiochemistry, Voyno-Yasenetsky Krasnoyarsk State Medical University, Krasnoyarsk, 660022, Russian Federation
Institute of Biophysics Siberian Branch of Russian Academy of Sciences, Krasnoyarsk, 660036, Russian Federation
Department of Human and Animal Physiology, Faculty of Medicine and Biology, Voronezh State University, Voronezh, 394018, Russian Federation
Department of Biological and Medical Physics, Moscow Institute of Physics and Technology, Moscow Region, Dolgoprudny, 141701, Russian Federation
Department of Biophysics, Faculty of Physics, Lomonosov Moscow State University, Moscow, 119991, Russian Federation
Laboratory of Medical Analytical Methods and Devices, Institute for Analytical Instrumentation of the Russian Academy of Sciences, St. Petersburg, 198095, Russian Federation
Sendai Viralytics LLC, Acton, MA 117261, United States
Laboratory of Cellular Bases for the Development of Malignant Diseases, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russian Federation

Доп.точки доступа:
Nechipurenko, Y. D.; Semyonov, D. A.; Lavrinenko, I. A.; Lagutkin, D. A.; Generalov, E. A.; Zaitceva, A. Y.; Matveeva, O. V.; Yegorov, Y. E.

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Positive feedback between acidosis and hypoxia during the transition of COVID-19 to a severe form of the disease / D. Lagutkin, D. Semyonov, Y. E. Yegorov [et al.] // FEBS Open Bio. - 2021. - Vol. 11. - P450-450. - Cited References:0 . - ISSN 2211-5463

РУБ Biochemistry & Molecular Biology

Аннотация: SARSCoV2 virus causes disease that has several distinctive characteristics compared to diseases caused by other viruses. We have put forward a hypothesis that relates COVID19 pathogenesis with acidosis, which frequently characterizes severe cases of this disease. It has been shown that hypoxia and acidosis affect the progression of severe COVID19 at various physiological levels such as organs, tissues, and cells. The physiological effects of acidosis and hypoxia range from the level of compensatory capabilities of the whole organism to the functioning of a single hemoglobin molecule. In our work, we consider several mechanisms that link the damaging factors of COVID19 with acidosis. These mechanisms reveal stepbystep processes with a pronounced positive feedback. In accordance with the well known Bohr effect, a decrease in blood pH leads to a drop in blood oxygen saturation. At the same time, this drop in saturation contributes to the further development of acidosis. This indicates a depletion of the body's compensatory capabilities to regulate acidosis and leads to deterioration of the patient's condition. In addition, a decrease in pH can cause conformational changes in the viral Sprotein, followed by changes in ability of some antibodies to recognize the virus. This might lead to the decrease in antibodies affinity and avidity, negatively affecting virus clearance. Low levels of pH and hypoxia in blood and tissues can induce a proinflammatory innate response even in the absence of antigen stimulation. Therefore, hypoxia and acidosis can lead to a restructuring of the immune system and multidirectional pro and antiinflammatory responses, which often, instead of recovery, lead to the disease aggravation.

WOS
Держатели документа:
Russian Acad Sci, Engelhardt Inst Mol Biol, Moscow, Russia.
Voyno Yasenetsky Krasnoyarsk State Med Univ, Krasnoyarsk, Russia.
Russian Acad Sci, Siberian Branch, Inst Biophys, Krasnoyarsk, Russia.
Voronezh State Univ, Voronezh, Russia.
Lomonosov Moscow State Univ, Fac Phys, 1-2 Leninskie Gory, Moscow 119991, Russia.
Russian Acad Sci, Inst Analyt Instrumentat, Moscow, Russia.
Sendai Viralyt LLC, Acton, MA USA.

Доп.точки доступа:
Lagutkin, D.; Semyonov, D.; Yegorov, Y. E.; Lavrinenko, I.; Generalov, E.; Zaitceva, A. Y.; Matveeva, O.; Nechipurenko, Y. D.

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