Revisiting the COVID-19 fatality rate and altitude association through a comprehensive analysis

Abstract

The emergence of COVID-19 virus has led to a pandemic with staggering morbidity and mortality. There is evidence showing that pre-existing conditions and environmental factors are associated with worse COVID-19 outcomes. Among these conditions, altitude is of particular interest. Altitude has been shown to influence the morbidity and mortality of multiple chronic pathologies such as cardiovascular disease, chronic obstructive pulmonary disease and lung cancer. COVID-19 fatality rate has been associated with as altitude as well, but findings are disputed. Therefore, we revisit this assessment with a comprehensive analysis of the relationship between COVID-19 fatality rates and altitude for the Mountain region of the United States while considering the effect of additional comorbidities and sociodemographic factors. A Generalized Additive Model (GAM) approach using one year of county data adjusted by population density was performed to evaluate associations within states and for the whole region. Our analysis revealed a consistent effect where COVID-19 case-fatality rate is decreased with higher altitude, even when controlling for pre-existing conditions and certain demographic variables. In summary, the work presented provides evidence that suggests that the protective effects of high altitude are likely to be influenced by physiologic factors but demographic trends that are associated with life at high altitude must also be considered.

Risk factors for persistent tomographic abnormalities at 6 months of follow-up in a cohort of hospitalized patients with moderate and severe COVID-19 living at high altitude

“…Due to Bogotá’s location at 2,640 m above sea level, PaO 2 is around 60 mmHg and SaO 2 is 90% in normal patients, with significant desaturations during exercise in patients with interstitial lung disease ( 11 ). Despite these lower saturations at altitude, different studies suggest that this does not represent a negative impact on the mortality of patients with COVID-19 residing at high altitudes ( 37 ).…”

Factors Associated with COVID-19 Death in a High-Altitude Peruvian Setting during the First 14 Months of the Pandemic: A Retrospective Multicenter Cohort Study in Hospitalized Patients

“…Physiological adaptations and genetic characteristics of individuals who live at high altitudes have been described as factors associated with lower mortality, higher probability of hospital discharge, and higher survival [ 34 , 39 , 40 , 41 , 42 , 43 ]. Notably, the most widely described factors that could account for the lower mortality rates in high-altitude populations are as follows: the hypobaric hypoxia in response to long-term exposure to high altitude and the resulting improved lung capacity, the reduced expression of the angiotensin-converting enzyme, and the higher levels of inflammatory cytokines (such as IL-6 y TNFα), hemoglobin, and erythropoietin [ 39 , 40 , 44 , 45 ]. It has also been reported that, compared to individuals residing in low-altitude areas, COVID-19 cases residing in high-altitude areas may present with low levels of fibrinogen and platelets, and disturbed electrolyte levels [ 46 ].…”

COVID-19 Mortality Is Attenuated at High Tropical and Subtropical Altitude: An Observational Study of a Database Covering Five Latin American Countries

“…However, subsequent reports have shown that COVID-19 infection rates are lower at higher altitudes 5,[7][8][9][10][11][12][13][14][15] . As it concerns mortality, findings remain unclear [16][17][18][19] but again have been attributed to the low population density at high-altitude 20 . Thus, a comprehensive analysis of the relationship between COVID-19 mortality and altitude was conducted for the highlands of the United States.…”