Re: "Mortality Attributed to COVID-19 in High-Altitude Populations" by Woolcott and Bergman

High Altitude Medicine & BiologyVol. 22, No. 1 Letters to the EditorFree AccessRe: "Mortality Attributed to COVID-19 in High-Altitude Populations" by Woolcott and BergmanGustavo Zubieta-Calleja, Alfredo Merino-Luna, Natalia Zubieta-DeUrioste, N. Freddy Armijo-Subieta, Jorge Soliz, Christian Arias-Reyes, Raffo Escalante-Kanashiro, Jose Antonio Carmona-Suazo, Alberto López-Bascope, Jose Manuel Calle-Aracena, Murray Epstein, and Enrique MaraviGustavo Zubieta-CallejaAddress correspondence to: Gustavo Zubieta-Calleja, MD, High Altitude Pulmonary and Pathology Institute (HAPPI—IPPA), Pulmonary Department, Av. Copacabana Prolongación # 55, La Paz, Bolivia E-mail Address: [email protected]High Altitude Pulmonary and Pathology Institute (HAPPI—IPPA), Pulmonary Department, La Paz, Bolivia.Search for more papers by this author, Alfredo Merino-LunaUniversidad Peruana de Ciencias Aplicadas (UPC), Lima, Perú.Search for more papers by this author, Natalia Zubieta-DeUriosteHigh Altitude Pulmonary and Pathology Institute (HAPPI—IPPA), Pulmonary Department, La Paz, Bolivia.Search for more papers by this author, N. Freddy Armijo-SubietaUniversidad Franz Tamayo, La Paz, Bolivia.Search for more papers by this author, Jorge SolizHigh Altitude Pulmonary and Pathology Institute (HAPPI—IPPA), Pulmonary Department, La Paz, Bolivia.Institut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Quebec City, Québec, Canada.Search for more papers by this author, Christian Arias-ReyesInstitut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Quebec City, Québec, Canada.Search for more papers by this author, Raffo Escalante-KanashiroUniversidad Peruana de Ciencias Aplicadas (UPC), Lima, Perú.Unidad de Cuidados Intensivos Instituto Nacional de Salud del Niño, Lima, Perú.Search for more papers by this author, Jose Antonio Carmona-SuazoHospital Juarez, Mexico City, Mexico.Search for more papers by this author, Alberto López-BascopeHospital Angeles Mexico, Mexico City, Mexico.Search for more papers by this author, Jose Manuel Calle-AracenaUniversidad Autónoma Tomas Frias, Potosí, Bolivia.Search for more papers by this author, Murray EpsteinUniversity of Miami Miller School of Medicine, Miami, Florida, USA.Search for more papers by this author, and Enrique MaraviProf. Emeritus, Intensive Care, Complejo Hospitalario de Navarra-O, Universidad de Navarra, Pamplona, España.Search for more papers by this authorPublished Online:29 Mar 2021https://doi.org/10.1089/ham.2020.0195AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookXLinked InRedditEmail Dear Editor,We have read with interest the article by Woolcott and Bergman, "Mortality Attributed to COVID-19 in High-Altitude Populations" (Woolcott and Bergman, 2020), and disagree with their conclusion that "Altitude is associated with COVID-19 mortality in men younger than 65 years." It is essential to contrast existing data from Bolivia and Peru to fully weigh the veracity of their conclusions.Their data overestimate the mortality risk due to underdiagnosis. According to COVID-19 diagnostic policies in the United States, Mexico, and other Latin American countries, tests were only performed in patients with evident symptoms. Such an approach can give rise to inaccurate data in many countries. The Mexican government's data are complex, and there were no travel restrictions between high and lowlands. Furthermore, quoting Woolcott, since "Kong demonstrated a higher proportion of asymptomatic COVID-19 cases in populations located >3,000 m than in those located at lower altitudes (*500–2,000 m)" (Woolcott and Bergman, 2020), then the ratio between deaths and confirmed cases increases with increasing altitude, diluting the case fatality rate. The total number of deaths (although inexact) can be used to calculate more precisely the total number of cases (asymptomatic+oligosymptomatic+severe+critical). All these relevant variables change the authors' incidence and mortality rate of COVID-19 completely.Only considering the analysis of counties and municipalities that reported deaths might be epidemiologically correct. However, it can lead to a case incidence miscalculation at altitude, as there is a risk of death in all regions affected by COVID-19. When analyzing the geographical distribution of illness, providing data on the absence of the studied feature (i.e., deaths per region) is important and must be considered in the final computation of the results and title.Moreover, their statement "Whether COVID-19 mortality rate is different in populations residing at low and high altitude remains unknown" (Woolcott and Bergman, 2020) is not accurate. Several recent publications and preprints document differences in mortality rates between altitude and lowlands (Rivero and Montoya 2020), peer-reviewed in Peru.In the United States, where there were no travel restrictions, confounding factor of acute ascent of travelers to high altitude with presymptomatic COVID-19 may pose an increased risk compared with highlanders. Tolerance to hypoxia increases with altitude and may be dependent on a higher hemoglobin in COVID-19 patients (Zubieta-Calleja et al., 2020). Table 1 presents data of all permanent residents in Bolivia with strict quarantine and no altitude changes.Table 1. Incidence, Mortality and Case Fatality in Bolivia and Peru during the COVID-19 PandemicAltitudesPopulation in millionsCOVID-19 incidence in %Mortality in %Case fatality rate in %Bolivia Lowlands <1500 m4.038.456.18.6 Moderate altitude 1500–2500 m3.252624.25.5 High altitude >2500 m4.3835.619.73.2Peru Lowlands <1500 m15.140.253.65.9 Moderate altitude 1500–2500 m4.523.228.73.5 High altitude >2500 m8.336.617.73.1The very low initial COVID-19 incidence documented in all high-altitude cities in Bolivia and Peru has been replicated in other parts of the world (data of 23 countries under peer review). Accinelli and Leon Barca (2020) found similar results in Peru. This has been attributed to several environmental and biological factors that may mitigate illness, including (1) high ultraviolet (UV) radiation, (2) dry air, (3) later appearance in high-altitude regions, (4) potential physiological factors such as a hypothesized reduced expression of angiotensin converting enzyme 2, a membrane enzyme to which the SARS-CoV-2 virus binds and gains entry into the cell, as detailed in a recent review (Danser et al., 2020). The initial slowly increasing slope of cases at high altitude has accelerated over time, nevertheless not to levels documented in lowland areas (Fig. 1). Pun et al. (2020) have highlighted that other environmental features, including seasonal weather patterns and temperature, at different latitudes may be important in viral transmission, which can explain why these results differ from those in Woolcott and Bergman's study of United States and Mexico outcomes. Zubieta et al. have also stressed the importance of UV radiation in the reduction of COVID-19 at high altitude (http://altitudeclinic.com/blog/2020/06/covid-19-pubs/).FIG. 1. Bolivia COVID-19 incidence cumulative data, March 10–October 8, 2020. The two main states (departments): La Paz (dashed blue line) and Santa Cruz (top green line), the latter with a 16% larger population than the first presented 26% more COVID-19 confirmed cases. Although the pandemic started almost simultaneously in both departments on March 10, there was a COVID-19 "lag" in high-altitude areas, replicated in many high-altitude cities in the world.We hope that the extensive data set presented herein will constitute a platform for enabling future clinical investigations of this important clinical disorder. According to these data, there is a clear tendency toward lower COVID-19 incidence and lower mortality at high altitude, for all ages in both countries compared with sea level (Table 1).Authors' ContributionsG.Z.-C. and N.Z.-D. generated the concept, wrote the article, and provided Figure 1. E.M. suggested writing the letter and approved it. A.M.-L. provided statistics from Peru in the table. N. F.A.S. provided statistics from Bolivia in the table. J.S., C.A.-R., and M.E. gave suggestions, structured, and edited the article. R.E.-K., A.L.-B., and J.M.C.-A. provided information on the subject. J.A.C.-S. provided insight into México. All authors have reviewed and accepted the final article.ReferencesAccinelli RA and Leon-Abarca JA. (2020). At high altitude COVID-19 is less frequent: The experience of Peru. Arch Bronconeumol 56:760–761. Crossref, Medline, Google ScholarDanser AHJ, Epstein M, and Batlle D. (2020). Renin-angiotensin system blockers and the COVID-19 pandemic: At present there is no evidence to abandon renin-angiotensin system blockers. Hypertension 75:1382–1385. Crossref, Medline, Google ScholarPun M, Turner R, Strapazzon G, Brugger H, and Swenson ER. (2020). Lower incidence of COVID-19 at high altitude: Facts and confounders. High Alt Med Biol 21:217–222. Link, Google ScholarRivero AC, and Montoya M. (2020). COVID19 en población residente de zonas geográficas a alturas superiores a 2500 msnm (in Spanish). SITUA 23:19–26. Google ScholarWoolcott OO, and Bergman RN. (2020). Mortality attributed to COVID-19 in high-altitude populations. High Alt Med Biol 21:409–416. Link, Google ScholarZubieta-Calleja GR, Zubieta-DeUrioste N, Venkatesh T, Das K, and Soliz J. (2020). COVID-19 and pneumolysis simulating extreme high-altitude exposure with altered oxygen transport physiology; multiple diseases, and scarce need of ventilators: Andean Condor' s-eye-view. Rev Recent Clin Trials [Epub ahead of print]; DOI: 10.2174/1574887115666200925141108. Crossref, Medline, Google ScholarFiguresReferencesRelatedDetailsCited byBiomarkers as predictors of mortality in critically ill obese patients with COVID-19 at high altitude6 April 2023 | BMC Pulmonary Medicine, Vol. 23, No. 1Mean Platelet Volu

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