Letters to the Editor Re: ''Mortality Attributed to COVID-19 in High-Altitude Populations'' by Woolcott and Bergman

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Letters to the Editor
Re: ‘‘Mortality Attributed to COVID-19 in High-Altitude
Populations’’ by Woolcott and Bergman
Gustavo Zubieta-Calleja,
1
Alfredo Merino-Luna,
2
Natalia Zubieta-DeUrioste,
1
N. Freddy Armijo-Subieta,
3
Jorge Soliz,
1,4
Christian Arias-Reyes,
4
Raffo Escalante-Kanashiro,
2,5
Jose Antonio Carmona-Suazo,
6
Alberto Lo´ pez-Bascope,
7
Jose Manuel Calle-Aracena,
8
Murray Epstein,
9
and Enrique Maravi
10
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 associ-
ated 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 under-
diagnosis. 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 (asymp-
tomatic+oligosymptomatic+severe+critical). All these rele-
vant variables change the authors’ incidence and mortality
rate of COVID-19 completely.
Only considering the analysis of counties and municipal-
ities 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 mor-
tality 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 restric-
tions, 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 resi-
dents in Bolivia with strict quarantine and no altitude
changes.
The 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 re-
sults in Peru. This has been attributed to several environ-
mental 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 ex-
pression 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
1
High Altitude Pulmonary and Pathology Institute (HAPPI—IPPA), Pulmonary Department, La Paz, Bolivia.
2
Universidad Peruana de Ciencias Aplicadas (UPC), Lima, Peru
´.
3
Universidad Franz Tamayo, La Paz, Bolivia.
4
Institut Universitaire de Cardiologie et de Pneumologie de Que
´bec, Laval University, Quebec City, Que
´bec, Canada.
5
Unidad de Cuidados Intensivos Instituto Nacional de Salud del Nin
˜o, Lima, Peru
´.
6
Hospital Juarez, Mexico City, Mexico.
7
Hospital Angeles Mexico, Mexico City, Mexico.
8
Universidad Auto
´noma Tomas Frias, Potosı
´, Bolivia.
9
University of Miami Miller School of Medicine, Miami, Florida, USA.
10
Prof. Emeritus, Intensive Care, Complejo Hospitalario de Navarra-O, Universidad de Navarra, Pamplona, Espan
˜a.
HIGH ALTITUDE MEDICINE & BIOLOGY
Volume 22, Number 1, 2021
ªMary Ann Liebert, Inc.
DOI: 10.1089/ham.2020.0195
102
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highlighted that other environmental features, including
seasonal weather patterns and temperature, at different lati-
tudes may be important in viral transmission, which can ex-
plain 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 radi-
ation in the reduction of COVID-19 at high altitude (http://
altitudeclinic.com/blog/2020/06/covid-19-pubs/).
We hope that the extensive data set presented herein
will constitute a platform for enabling future clinical in-
Table 1. Incidence, Mortality and Case Fatality in Bolivia and Peru during the COVID-19 Pandemic
Altitudes
Population
in millions
COVID-19
incidence in %
Mortality
in %
Case fatality
rate in %
Bolivia
Lowlands <1500 m 4.0 38.4 56.1 8.6
Moderate altitude 1500–2500 m 3.25 26 24.2 5.5
High altitude >2500 m 4.38 35.6 19.7 3.2
Peru
Lowlands <1500 m 15.1 40.2 53.6 5.9
Moderate altitude 1500–2500 m 4.5 23.2 28.7 3.5
High altitude >2500 m 8.3 36.6 17.7 3.1
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.
LETTER TO THE EDITOR 103
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vestigations 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’ Contributions
G.Z.-C. and N.Z.-D. generated the concept, wrote the
article, and provided Figure 1.E.M.suggestedwritingthe
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 Me
´xico. All authors have reviewed
and accepted the final article.
References
Accinelli RA and Leon-Abarca JA. (2020). At high altitude
COVID-19 is less frequent: The experience of Peru. Arch
Bronconeumol 56:760–761.
Danser 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.
Pun 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.
Rivero AC, and Montoya M. (2020). COVID19 en poblacio
´n
residente de zonas geogra
´ficas a alturas superiores a 2500
msnm (in Spanish). SITUA 23:19–26.
Woolcott OO, and Bergman RN. (2020). Mortality attributed to
COVID-19 in high-altitude populations. High Alt Med Biol
21:409–416.
Zubieta-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.
Address correspondence to:
Gustavo Zubieta-Calleja, MD
High Altitude Pulmonary
and Pathology Institute (HAPPI—IPPA)
Pulmonary Department
Av. Copacabana Prolongacio
´n # 55, La Paz
Bolivia
E-mail: gzubietajr@gmail.com
Received October 13, 2020;
accepted in final form November 20, 2020.
104 LETTER TO THE EDITOR
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