Kathmandu, May 8

Highlights:

- People living in altitude of over 2,500 metres are less susceptible to COVID-19

- Fewer highland inhabitants may have contracted COVID-19 due to hypoxia

- High-altitude environmental factors may have reduced the virulence of COVID-19

There’s good news for people living in high altitudes: they may be less susceptible to coronavirus infection. That’s the finding of the paper titled, ‘Does the pathogenesis of SAR-CoV-2 virus decrease at high-altitude?’, available in the National Library of Medicine of the United States.

This paper, written by Christian Arias-Reyes of University Institute of Cardiology and Respirology of Quebec, Canada, et al, has analysed epidemiological data of the Tibetan region of China, Bolivia and Ecuador.

The paper has defined high-altitude inhabitants as those living in altitudes of over 2,500 metres above the sea level. This means Nepalis living in places like Mustang, Manang and certain parts of Dolpa, to name a few, are less likely to contract the deadly coronavirus disease, which has so far killed over 257,000 and infected more than 3.7 million worldwide.

The reason for decreased severity of the global COVID-19 outbreak at high altitude could be related to environmental factors, says the paper.

A high-altitude environment is characterised by “drastic changes in temperature between night and day, air dryness, and high levels of ultraviolet (UV) light radiation” with “UV radiation acting as a natural sanitizer”. “These factors may dramatically reduce the survival capacity of the virus at high-altitude, and therefore its virulence,” says the paper. “Finally, due to the lower density of air and greater distance between molecules at high-altitude, the size of the airborne virus inoculum must be smaller than at sea level.”

These characteristics may provide explanation to why more coronavirus cases are being detected in lowlands, such as Udaypur and Nepalgunj, of Nepal. Nepal has detected 101 coronavirus cases so far, of which over 90 per cent are from Tarai, located at an altitude of up to 300 metres, and inner Tarai.

Like in Nepal, the study found that COVID-19 infection rates were very low in highlands of China, Bolivia and Ecuador. In the plateau region of China, which covers Tibet, Qinghai and part of Sichuan, only 134 confirmed cases have been reported, which is drastically low than in other parts of the country. The results were similar in Bolivia and Ecuador. Bolivia reported three-fold lower cases in high-altitude regions than in lowlands, whereas Ecuador registered four-fold less COVID-19 cases in high-altitude areas than in lowlands.

“Although these results are encouraging, the bitter truth is that not many Nepalis live in high-altitude areas [because of limited access to road network, markets and various amenities]. So the study is not relevant for Nepal,” said Dr Kiran Raj Pandey, a physician and public health expert currently associated with HAMS Hospital.

Although over 1,200 settlements are located at altitude of over 3,000 metres in Nepal, half of the Nepalis live in lowlands called Tarai. Another 43 per cent of Nepalis live in hilly areas, like Kathmandu and Pokhara, which are located at an altitude of around 1,400 metres. But the study in Bolivia found that people living in altitude of 1,866 metres in a city called Tarjia had reported relatively little transmission of disease.

So why is transmission of COVID-19 low in highlands?

COVID-19 is an infection caused by coronavirus. The outer layer of the coronavirus consists of spike proteins. Once the virus enters the body, the spike proteins look for receptor called angiotensin-converting enzyme 2 (ACE-2) in human cell. ACE-2 allows the virus to enter the human cell. Once inside, the virus releases its RNA, turning the human cell into a factory to produce more coronavirus. This completely destroys the human cell. Once the cell is destroyed, the viruses then move out to other cells to repeat the process of generating more coronavirus.

This means “reducing the activity of ACE-2 in [human] cell membranes could theoretically reduce the ability of SARS-CoV-2 to penetrate [human] cells, says the paper. And high altitude does just that. It makes ACE-2 less active while making ACE-1 more energetic. ACE-1 generally becomes more receptive when there is deficiency in the amount of oxygen that reaches the tissues -- a medical condition known as hypoxia.

“ACE-1 is upregulated by the hypoxia-inducible factor 1 (HIF-1), a master regulator of the response to hypoxia, in human pulmonary artery smooth muscle cells,” says the paper, adding, “Similar results were obtained in rats exposed to conditions equivalent to 4,500 meters of altitude. After 28 days in that altitude, the heart cells of rats showed increased levels of ACE-1 and decreased expression of ACE-2.”

These findings suggest that high-altitude inhabitants “express reduced levels of ACE-2 in their lungs and other tissues”. “Thus, adaptation to high-altitude environment could render local inhabitants less susceptible to SARS-CoV-2 virus and consequently are protected from the development of the disease defining acute respiratory distress syndrome,” says the paper.