Does the pathogenesis of SARS-CoV-2 virus decrease at high-altitude?
Christian Arias-Reyes, Natalia Zubieta-DeUrioste, Liliana Poma-Machicao, Fernanda Aliaga-Raduan, Favio Carvajal-Rodriguez, Mathias Dutschmann, Edith M Schneider-Gasser, Gustavo Zubieta-Calleja, Jorge Soliz, Christian Arias-Reyes, Natalia Zubieta-DeUrioste, Liliana Poma-Machicao, Fernanda Aliaga-Raduan, Favio Carvajal-Rodriguez, Mathias Dutschmann, Edith M Schneider-Gasser, Gustavo Zubieta-Calleja, Jorge Soliz
Abstract
In the present study we analyze the epidemiological data of COVID-19 of Tibet and high-altitude regions of Bolivia and Ecuador, and compare to lowland data, to test the hypothesis that high-altitude inhabitants (+2,500 m above sea-level) are less susceptible to develop severe adverse effects in acute SARS-CoV-2 virus infection. Analysis of available epidemiological data suggest that physiological acclimatization/adaptation that counterbalance the hypoxic environment in high-altitude may protect from severe impact of acute SARS-CoV-2 virus infection. Potential underlying mechanisms such as: (i) a compromised half-live of the virus caused by the high-altitude environment, and (ii) a hypoxia mediated down regulation of angiotensin-converting enzyme 2 (ACE2), which is the main binding target of SARS-CoV-2 virus in the pulmonary epithelium are discussed.
Keywords: COVID-19; Hypoxia; Lung remodeling; UV.
Copyright © 2020. Published by Elsevier B.V.
Figures


References
- Andrade M. Pagina siete; Bolivia: 2020. La radiación ultravioleta en tiempos de cuarentena.
- Cohen J.E., Small C. Hypsographic demography: the distribution of human population by altitude. Proc. Natl. Acad. Sci. U. S. A. 1998;95(24):14009–14014. doi: 10.1073/pnas.95.24.14009.
- Dang Z., Su S., Jin G., Nan X., Ma L., Li Z., Lu D., Ge R. Tsantan Sumtang attenuated chronic hypoxia-induced right ventricular structure remodeling and fibrosis by equilibrating local ACE-AngII-AT1R/ACE2-Ang1-7-Mas axis in rat. J. Ethnopharmacol. 2020;250:112470. doi: 10.1016/j.jep.2019.112470.
- Gelek L. Radio Free Asia; 2020. Schools in Tibet to Reopen as COVID-19 Fears Subside.
- Gobierno-de-la-Republica-de-Ecuador . 2020. Coronavirus Ecuador.
- Hamming I., Timens W., Bulthuis M.L., Lely A.T., Navis G., van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J. Pathol. 2004;203(2):631–637. doi: 10.1002/path.1570.
- Hampl V., Herget J., Bibova J., Banasova A., Huskova Z., Vanourkova Z., Jichova S., Kujal P., Vernerova Z., Sadowski J., Cervenka L. Intrapulmonary activation of the angiotensin-converting enzyme type 2/angiotensin 1-7/G-protein-coupled Mas receptor axis attenuates pulmonary hypertension in Ren-2 transgenic rats exposed to chronic hypoxia. Physiol. Res. 2015;64(1):25–38.
- Hijmans R.J., Cameron S.E., Parra J.L., Jones P.G., Jarvis A. Very high resolution interpolated climate surfaces for global land areas. Int. J. Climatol. 2005;25:1965–1978.
- Instituto-Nacional-de-Estadística . 2018. Producto Interno Bruto Departamental (ID TABLA: 4020301)
- Jia H.P., Look D.C., Shi L., Hickey M., Pewe L., Netland J., Farzan M., Wohlford-Lenane C., Perlman S., McCray P.B., Jr. ACE2 receptor expression and severe acute respiratory syndrome coronavirus infection depend on differentiation of human airway epithelia. J. Virol. 2005;79(23):14614–14621. doi: 10.1128/JVI.79.23.14614-14621.2005.
- Kimakova P., Solar P., Solarova Z., Komel R., Debeljak N. Erythropoietin and its angiogenic activity. Int. J. Mol. Sci. 2017;18(7) doi: 10.3390/ijms18071519.
- Lei Y., Huang X., Lang B., Lan Y., Lu J., Zeng F. Clinical features of imported cases of coronavirus disease 2019 in Tibetan patients in the Plateau area. MedRxiv. 2020 doi: 10.1101/2020.03.09.20033126.
- Lu R., Zhao X., Li J., Niu P., Yang B., Wu H., Wang W., Song H., Huang B., Zhu N., Bi Y., Ma X., Zhan F., Wang L., Hu T., Zhou H., Hu Z., Zhou W., Zhao L., Chen J., Meng Y., Wang J., Lin Y., Yuan J., Xie Z., Ma J., Liu W.J., Wang D., Xu W., Holmes E.C., Gao G.F., Wu G., Chen W., Shi W., Tan W. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395(10224):565–574. doi: 10.1016/S0140-6736(20)30251-8.
- Lundby C., Thomsen J.J., Boushel R., Koskolou M., Warberg J., Calbet J.A., Robach P. Erythropoietin treatment elevates haemoglobin concentration by increasing red cell volume and depressing plasma volume. J. Physiol. 2007;578(Pt 1):309–314. doi: 10.1113/jphysiol.2006.122689.
- Ministerio-de-Comunicación . 2020. COVID-19 Bolivia. Gaceta Oficial.
- Ministerio-de-Comunicación . Portal de información estatal; 2017. El Alto es la segunda ciudad con más población de Bolivia Publicación ENLACE.
- Prensa-Latina . Agencia Informativa Latinoamericana; 2020. Santa Cruz departamento de Bolivia con mas casos de COVID-19.
- Ren L.L., Wang Y.M., Wu Z.Q., Xiang Z.C., Guo L., Xu T., Jiang Y.Z., Xiong Y., Li Y.J., Li X.W., Li H., Fan G.H., Gu X.Y., Xiao Y., Gao H., Xu J.Y., Yang F., Wang X.M., Wu C., Chen L., Liu Y.W., Liu B., Yang J., Wang X.R., Dong J., Li L., Huang C.L., Zhao J.P., Hu Y., Cheng Z.S., Liu L.L., Qian Z.H., Qin C., Jin Q., Cao B., Wang J.W. Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study. Chin. Med. J. (Engl.) 2020 doi: 10.1097/CM9.0000000000000722. [Epub ahead of print]
- Rothan H.A., Byrareddy S.N. The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak. J. Autoimmun. 2020 doi: 10.1016/j.jaut.2020.102433.
- Soliz J., Joseph V., Soulage C., Becskei C., Vogel J., Pequignot J.M., Ogunshola O., Gassmann M. Erythropoietin regulates hypoxic ventilation in mice by interacting with brainstem and carotid bodies. J. Physiol. 2005;568(Pt2):559–571.
- Tseten T. Central Tibetan Administration; 2020. Wuhan Coronavirus: A Growing Concern for Tibetans Inside Tibet.
- United-States-Environmental-Protection-Agency . 2017. Calculating the UV Index.
- van Doremalen N., Bushmaker T., Morris D.H., Holbrook M.G., Gamble A., Williamson B.N., Tamin A., Harcourt J.L., Thornburg N.J., Gerber S.I., Lloyd-Smith J.O., de Wit E., Munster V.J. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. N. Engl. J. Med. 2020 doi: 10.1056/NEJMc2004973.
- World-Health-Organization . 2020. Rolling Updates on Coronavirus Disease (COVID-19)
- Wu T. The Qinghai–Tibetan Plateau: how high do Tibetans live? High Alt. Med. Biol. 2001;2(4):489–499.
- Xu B., Gutierrez B., Mekaru S., Sewalk K., Goodwin L., Loskill A., Cohn E.L., Hswen Y., Hill S.C., Cobo M.M., Zarebski A.E., Li S., Wu C.H., Hulland E., Morgan J.D., Wang L., O’Brien K., Scarpino S.V., Brownstein J.S., Pybus O.G., Pigott D.M., Kraemer M.U.G. Epidemiological data from the COVID-19 outbreak, real-time case information. Sci. Data. 2020;7(1):106. doi: 10.1038/s41597-020-0448-0.
- Zhang R., Wu Y., Zhao M., Liu C., Zhou L., Shen S., Liao S., Yang K., Li Q., Wan H. Role of HIF-1alpha in the regulation ACE and ACE2 expression in hypoxic human pulmonary artery smooth muscle cells. Am. J. Physiol. Lung Cell Mol. Physiol. 2009;297(4):L631–640. doi: 10.1152/ajplung.90415.2008.
- Zubieta-Calleja G. 2020. Covid-19 Pandemia Essential Suggestions.
- Zubieta-Calleja G. 2020. Las ventajas de la radiación ultravioleta en el control del coronavirus en la altura. La razon.
- Zubieta-Calleja G.R., Zubieta-DeUrioste N.A. Extended longevity at high altitude: benefits of exposure to chronic hypoxia. Blde Univ. J. Health Sci. 2017;2(2):80–90.
Source: PubMed
다가오는 임상 시험
-
NCT07931924아직 모집하지 않음요실금 | 신경성 방광 | 요로 전환 | 골반 악성종양 | 방광암
-
NCT07932964모병정상적인 청력 | 소음 노출 | Preferred Loudness Level
-
NCT07933419아직 모집하지 않음투명 세포 신장 세포 암종 | 난소 암 | 기타 진행성 고형 종양
-
NCT07931144아직 모집하지 않음
-
NCT07889232아직 모집하지 않음전이성 비소세포폐암 | Cancer-Associated Weight Loss | Elevated Inflammatory Markers
-
NCT07931534아직 모집하지 않음비대 | 편도선 절제술 | 기도 폐쇄 갑피 | 아데노이드절제술
-
NCT07933536아직 모집하지 않음
-
NCT07933185모병턱 낭종 | Alveolar Bone Defects