Does the pathogenesis of SARS-CoV-2 virus decrease at high-altitude?

In the present study we analyze the epidemiological data of COVID-19 of Tibet and high-altitude regions of Bolivia and Ecuador, and compare to lowland data, to test the hypothesis that high-altitude inhabitants (+2,500 m above sea-level) are less susceptible to develop severe adverse effects in acute SARS-CoV-2 virus infection. Analysis of available epidemiological data suggest that physiological acclimatization/adaptation that counterbalance the hypoxic environment in high-altitude may protect from severe impact of acute SARS-CoV-2 virus infection. Potential underlying mechanisms such as: (i) a compromised half-live of the virus caused by the high-altitude environment, and (ii) a hypoxia mediated down regulation of angiotensin-converting enzyme 2 (ACE2), which is the main binding target of SARS-CoV-2 virus in the pulmonary epithelium are discussed.

The overlooked significance of plasma volume for successful adaptation to high altitude in Sherpa and Andean natives.

In contrast to Andean natives, high-altitude Tibetans present with a lower hemoglobin concentration that correlates with reproductive success and exercise capacity. Decades of physiological and genomic research have assumed that the lower hemoglobin concentration in Himalayan natives results from a blunted erythropoietic response to hypoxia (i.e., no increase in total hemoglobin mass). In contrast, herein we test the hypothesis that the lower hemoglobin concentration is the result of greater plasma volume, rather than an absence of increased hemoglobin production. We assessed hemoglobin mass, plasma volume and blood volume in lowlanders at sea level, lowlanders acclimatized to high altitude, Himalayan Sherpa, and Andean Quechua, and explored the functional relevance of volumetric hematological measures to exercise capacity. Hemoglobin mass was highest in Andeans, but also was elevated in Sherpa compared with lowlanders. Sherpa demonstrated a larger plasma volume than Andeans, resulting in a comparable total blood volume at a lower hemoglobin concentration. Hemoglobin mass was positively related to exercise capacity in lowlanders at sea level and in Sherpa at high altitude, but not in Andean natives. Collectively, our findings demonstrate a unique adaptation in Sherpa that reorientates attention away from hemoglobin concentration and toward a paradigm where hemoglobin mass and plasma volume may represent phenotypes with adaptive significance at high altitude.

SLC2A9 and ZNF518B polymorphisms correlate with gout-related metabolic indices in Chinese Tibetan populations.

Current evidence suggests that heredity and metabolic syndrome contribute to gout progression. SLC2A9 and ZNF518B may play a role in gout progression in different populations, but no studies have focused on the Tibetan Chinese population. In this study, we determined whether variations in these 2 genes were correlated with gout-related indices in Chinese-Tibetan gout patients. We detected 6 single nucleotide polymorphisms in SLC2A9 and ZNF518B in 319 Chinese Tibetan gout patients. One-way analysis of variance was used to evaluate the polymorphisms' effects on gout based on mean serum levels of metabolism indicators. Polymorphisms in SLC2A9 and ZNF518B affected multiple risk factors related to gout development. Significant differences in serum triglyceride levels and high-density lipoprotein-cholesterol level were detected between different genotypic groups with SLC2A9 polymorphisms rs13129697 (P = 0.022), rs4447863 (P = 0.018), and rs1014290 (P = 0.045). Similarly in ZNF518B, rs3217 (P = 0.016) and rs10016022 (P = 0.046) were associated with high creatinine and glucose levels, respectively. This study is the first to investigate and identify positive correlations between SLC2A9 and ZNF518B gene polymorphisms and metabolic indices in Tibetan gout patients. We found significant evidence indicating that genetic polymorphisms affect gout-related factors in Chinese Tibetan populations.

Molecular analysis of the thiopurine S-methyltransferase alleles in Bolivians and Tibetans.

BACKGROUND: Thiopurine drugs are used as immunosuppressant or cytotoxic drugs. Thiopurine S-methyltransferase (TPMT) methylates and thereby modulates the therapeutic and toxic effects of these drugs. The activity of TPMT is affected by genetic polymorphism of TPMT alleles, and these alleles have not been studied in Tibetans and Bolivians. OBJECTIVES: To analyse the TPMT allelic frequencies in Tibetans and Bolivians. METHODS: We developed an inexpensive method for collecting blood and extracting genomic DNA. Genomic DNA was extracted from blood spots of 50 Tibetans and 115 Bolivians. The frequencies of allelic variants of TPMT gene (TPMT*1 to TPMT*8) were determined using polymerase chain reaction-restriction fragment length polymorphism technique. RESULTS: The allelic frequencies of TPMT*1 were 99 and 93.48% for Tibetans and Bolivians, respectively. The corresponding allelic frequencies of TPMT*3A were 0 and 6.52% and those of TPMT*3C were 1.0 and 0%. No TPMT*2, 3B, 3D, 4-8 were found in these two populations. CONCLUSIONS: As with Caucasian populations, TPMT*3A is the most prevalent mutant allele in Bolivians. Our results may be of value in helping to guide the prescription of thiopurine drugs in these populations.

Syndromes of subacute mountain sickness.

Two clinical syndromes, acute and chronic mountain sickness, have traditionally been associated with high altitude. Recently, two separate entities of subacute nature have been described in infants and adults. In this paper, we review the published literature on these conditions. Subacute infantile mountain sickness is a condition seen predominantly in Han Chinese infants living in Tibet, although it has been described in other high altitude communities as well. It came into prominence only after the large-scale migration of Chinese population from the low altitude of mainland China to the high altitudes of the Qinghai-Tibetan plateau. The condition is characterized by features of severe hypoxic pulmonary hypertension and heart failure. Pulmonary histology is consistent with muscularization of the pulmonary arterioles, but no intimal proliferation or plexiform lesions are seen. The second syndrome, adult subacute mountain sickness, has been described almost exclusively in Indian soldiers living at extreme altitude for prolonged periods of time. In this condition also, hypoxic pulmonary hypertension appears to be the dominant factor responsible for severe congestive heart failure. Both these conditions have several similarities with brisket disease in cattle; hypoxic pulmonary vasoconstriction plays an important role in the pathogenesis, and removal from high altitude results in complete resolution. Thus, it appears that both these syndromes are human counterparts of brisket disease in cattle.