People living at high altitude are less likely to experience the worst effects of coronavirus than those at sea level, a new study suggests.
Those on higher ground are better adapted to low levels of oxygen in the blood – which is one potentially fatal effect of SARS-CoV-2 infection, scientists say.
Researchers compared cases of COVID-19 in the high and low lands of Bolivia and Ecuador in South America and Tibet, a mountainous region covering China.
High-altitude inhabitants exposed to low oxygen, or ‘hypoxic’, conditions have become biologically accustomed through improved oxygen transport in the arteries.
They also express reduced levels of the ACE2 enzyme – which the virus needs to infect host cells – in lungs and other tissues.
Environmental factors such as increased UV radiation higher up may also act as a ‘natural sanitiser’ higher up, the scientists claim.
Covid-19 infection rates at high-altitude regions are about three-fold lower than the lowlands in Bolivia and four-fold lower in Ecuador.
And despite its relative proximity to Wuhan, the epicentre of the pandemic, the general prevalence of infection in Tibet ‘does not correspond to global trends’.
Tibetan Fort on top of the rocky hill in Gyangze in central Tibet. The general prevalence of infection in Tibet ‘does not correspond to global trends’, researchers say
Geographic and altitudinal distribution of COVID-19 pandemic in China. The blue dots represent COVID-19 positive cases. Geographic coordinates were retrieved from the real-time database on March 30.
Researchers also analysed real-time geographic data of the COVID-19 pandemic globally to find a clear decrease in affected populations living above 9,800 feet (3,000 metres) above sea level.
‘At sea-level, when people get coronavirus and their lungs get destroyed, it is as if they are climbing Mount Everest in just a couple of days, without oxygen,’ study co-author Gustavo Zubieta-Calleja, director of Bolivia’s High Altitude Pulmonary and Pathology Institute, told the FT.
HYPOXIA: BODY TISSUES DEPRIVED OF OXYGEN
Hypoxia, in biology and medicine, condition of the body in which the tissues are starved of oxygen.
Diseases of the blood, the heart and circulation, and the lungs may all produce some form of hypoxia.
On a molecular level, cells respond and adapt to hypoxia by increasing levels of a molecule known as hypoxia-inducible factor (HIF).
Elevated HIF levels enable cells to survive and proliferate despite reduced oxygen availability.
In its extreme form, where oxygen is entirely absent, hypoxia is known as anoxia.
Hypoxia differs from hypoxemia and anoxemia, which refer to states that have low or zero arterial oxygen supply.
Source: Encyclopedia Britannica
But people at high altitude are physically adapted to lower levels of oxygen in the blood through increased ventilation, augmented arterial oxygen transport and higher tissue oxygenation, Zubieta-Calleja and his team claims.
These factors could be explored as potential therapy for people suffering from the adverse respiratory effects of Covid-19.
Researchers analysed data from the Tibetan region of China, where the peak of the epidemic is over; Bolivia, one of the last countries affected by the pandemic, which has a third of its territory extended at high-altitude; and Ecuador, a country deeply affected by the pandemic, in which half of the population lives at high-altitude areas.
In Bolivia, researchers compared the high-altitude regions of La Paz, at a range of 7,800 to 13,000 feet (2,400 to 4,000 metres) above sea level, and Oruro, 12,000 feet (3,735 metres) above sea level, with lower regions, predominantly Santa Cruz, which stands on the Pirai River in the tropical lowlands.
They registered a total of 54 cases in Bolivian provinces located at high-altitude and 140 below 8,200 feet (2,500 metres) until April 7 – approximately a three-fold increase.
‘The low rate of infection in Bolivia’s high-altitude population is remarkable and clearly does not follow the often exponential infection rates reported in many countries,’ the team said.
Bolivian data is in line with data reported in Ecuador, a Latin American country that is severely affected by the pandemic, they claim.
As of April 7, four-fold fewer Covid-19 cases were in high-altitude areas of Ecuador (7,114,300 inhabitants) with only 722 cases, compared to 2,943 cases in the coastal regions (8,328,300 inhabitants).
Cityscape of La Paz in Bolivia. High-altitude inhabitants that are chronically exposed to hypoxic conditions express reduced levels of the ACE2 enzyme – which the virus needs to infect host cells – in lungs and other tissues
Geographic altitudinal distribution of COVID-19 pandemic in Bolivia. The blue dots represent COVID-19 positive cases. The region of Santa Cruz had been harder hit that the more elevated regions in the west
As for Tibet, the region’s capital, Lhasa, is located at an elevation of about 11,400 feet above sea level, or 3,500 metres above sea level.
While the road distance between Lhasa and Wuhan, the location of the very first Covid-19 cases, is more than 2,000 miles, they are connected by train and bus, which indicates ‘tourist and commercial exchange between these cities may be considerable’, the researchers said.
But imported cases of COVID-19 in Tibetan patients were generally mild in this high-altitude area.
Only 134 confirmed cases were reported for the plateau region consisting of Tibet, Qinghai and part of Sichuan.
A representative cohort of 67 patients who were diagnosed with COVID-19 in Sichuan reveals that 54 per cent were completely asymptomatic – meaning they had no cough, fever, or headache – and less than 10 per cent presented fever, despite almost a third being at high risk.
All of these patients fully recovered after treatment, resulting in no mortality, the researchers add.
The team suggest both environmental and physiological factors for the decreased severity of the global COVID-19 outbreak at high altitude.
As well as an increased physical adaptation to low oxygen, there is a positive correlation between the infection rate of SARS-CoV-1 – a strain of coronavirus that caused previous outbreaks – and ACE2 in pulmonary epithelial cells.
Previous studies also show both SARS-CoV-1 – which caused the Sars outbreak of 2002 to 2004 – and SARS-CoV-2 – which causes Covid-19 – bind to ACE2.
A decrease of ACE2 expression in high-altitude could represent a ‘physiological protective’ for the lethal swelling of the lungs.
There is as yet ‘no evidence of an underlying physiological mechanism’ that could affect severity of infection, however, the team say.
Global distribution of Covid-19 cases is higher overall at lower altitudes. The number of cases show a distinct decrease when the affected population lives at an altitude of above 9,800 feet (3,000 metres) above sea level
But environmental altitude factors, including drastic changes in temperature between night and day, air dryness, and high levels of ultraviolet (UV) light radiation, may also play a part.
UV light radiation are known to be capable of producing alterations in the molecular bonds of the DNA and RNA, and so UV radiation at high-altitude may act as a free and abundant ‘sanitizer’.
Also, due to the lower density of air and greater distance between molecules at high-altitude, the size of the airborne virus must be smaller than at sea level, they say., which may also play a part in the distribution of cases.
Zubieta-Calleja acknowledged other factors such as diet, lifestyle, chronic diseases, age and obesity are likely to influence the statistics used in the study, which also used data gained in March and April.
He also stressed to the FT that those living at altitude should continue to wash hands thoroughly and wear face masks.
The research paper, which has been published in Respiratory Physiology & Neurobiology, links to updated versions of Bolivia’s Covid-19 cases by region until the end of the pandemic.