Decreased incidence, virus transmission capacity, and severity of COVID-19 at altitude on the American continent

Arias‐Reyes, Christian; Carvajal-Rodriguez, Favio; Poma-Machicao, Liliana; Aliaga‐Raduán, Fernanda; Marques, Danuzia A.; Zubieta-DeUrioste, Natalia; Accinelli, Roberto A.; Schneider‐Gasser, Edith M.; Zubieta-Calleja, Gustavo; Dutschmann, Mathias; Soliz, Jorge

doi:10.1371/journal.pone.0237294

Cited by 30 publications

(24 citation statements)

References 31 publications

(32 reference statements)

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“…In this work, all the data were normalized by population density [ 6 ]. These results were confirmed in a subsequent study [ 9 ].…”

Section: Discussionsupporting

confidence: 80%

“…Altitude exerts a protective effect for the development of diabetes, hypertension and obesity, comorbidities that may worsen the outcome of COVID-19 [ 62 ]. Also, the size of the virus inoculum in the air should gradually decrease as the barometric pressure decreases and the distance among air molecules increases [ 9 ]. Furthermore, expression of pulmonary ACE2 appears to decrease under physiological conditions of chronic hypoxia such as those found in high-altitude settings [ 6 , 10 , 11 ].…”

Section: Discussionmentioning

confidence: 99%

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Diabetes increases the risk of COVID-19 in an altitude dependent manner: An analysis of 1,280,806 Mexican patients

et al. 2021

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Aims The objective of this study is to analyze how the impact of Diabetes Mellitus [DM] in patients with COVID-19 varies according to altitudinal gradient. Methods We obtained 1,280,806 records from adult patients with COVID-19 and DM to analyze the probability of COVID-19, development of COVID-19 pneumonia, hospitalization, intubation, admission to the Intensive Care Unit [ICU] and case-fatality rates [CFR]. Variables were controlled by age, sex and altitude of residence to calculate adjusted prevalence and prevalence ratios. Results Patients with DM had a 21.8% higher prevalence of COVID-19 and an additional 120.2% higher prevalence of COVID-19 pneumonia. The adjusted prevalence was also higher for these outcomes as well as for hospitalization, intubation and ICU admission. COVID-19 and pneumonia patients with DM had a 97.0% and 19.4% higher CFR, respectively. With increasing altitudes, the probability of being a confirmed COVID-19 case and the development of pneumonia decreased along CFR for patients with and without DM. However, COVID-19 patients with DM were more likely to require intubation when residing at high altitude. Conclusions The study suggests that patients with DM have a higher probability of being a confirmed COVID-19 case and developing pneumonia. Higher altitude had a protective relationship against SARS-CoV-2 infection; however, it may be associated with more severe cases in patients with and without DM. High altitude decreases CFR for all COVID-19 patients. Our work also shows that women are less affected than men regardless of altitude.

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“…In this work, all the data were normalized by population density [ 6 ]. These results were confirmed in a subsequent study [ 9 ].…”

Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Diabetes increases the risk of COVID-19 in an altitude dependent manner: An analysis of 1,280,806 Mexican patients

et al. 2021

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“…This brief communication reports the development of an "In-House" ELISA that is being used to survey seroprevalence in our region, and has uncovered that inhabitants of Tafí del Valle, a village situated in the Andean foothills at more than 2,000 meters above median sea level (mamsl), showed significantly higher anti-RBD titers than the population of San Miguel de Tucumán, located around 400 mamsl. To our knowledge, this is the first study showing an increased antibody response against SARS-CoV-2 in highaltitude individuals, adding more evidence regarding the effect of altitude on the interplay between this novel coronavirus, the immune system and the outcome of the infection (5)(6)(7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 78%

“…Recent epidemiological data have been used to propose that altitude of residence may not only influence those environmental features considered key to lesser viral transmission, but also susceptibility to more severe forms of COVID-19 through hypoxic-hypobaria driven genomic or non-genomic adaptations specific to high-altitude populations (30)(31)(32). Accordingly, Arias-Reyes et al (5,7), have reported a lower absolute number of COVID-19 cases at higher altitudes in Bolivia and Tibet. A similar protective effect was described in Bogotá by Cano-Pérez et al (33).…”

Section: Discussionmentioning

confidence: 99%

Elevated Humoral Immune Response to SARS-CoV-2 at High Altitudes Revealed by an Anti-RBD “In-House” ELISA

et al. 2021

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The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a global pandemic with dramatic health and socioeconomic consequences. The Coronavirus Disease 2019 (COVID-19) challenges health systems to quickly respond by developing new diagnostic strategies that contribute to identify infected individuals, monitor infections, perform contact-tracing, and limit the spread of the virus. In this brief report, we developed a highly sensitive, specific, and precise “In-House” ELISA to correctly discriminate previously SARS-CoV-2-infected and non-infected individuals and study population seroprevalence. Among 758 individuals evaluated for anti-SARS-CoV-2 serology in the province of Tucumán, Argentina, we found a weak correlation between antibodies elicited against the RBD, the receptor-binding domain of the Spike protein, and the nucleocapsid (N) antigens of this virus. Additionally, we detected mild levels of anti-RBD IgG antibodies in 33.6% of individuals diagnosed with COVID-19, while only 19% showed sufficient antibody titers to be considered as plasma donors. No differences in IgG anti-RBD titers were found between women and men, neither in between different age groups ranging from 18 to 60. Surprisingly, individuals from a high altitude village displayed elevated and longer lasting anti-RBD titers compared to those from a lower altitude city. To our knowledge, this is the first report correlating altitude with increased humoral immune response against SARS-CoV-2 infection.

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“…This phenomenon, which we coined ‘hypoxia paradox’, likely contributes to unfavorable outcomes in COVID-19. Along these lines of thought, people living at high-altitude have elevated levels of serum EPO and are therefore believed to be better protected from a severe course of COVID-19 (Arias-Reyes et al 2020 , 2021 ; Beall 2007 ; Jaramillo et al 2021 ; Soliz et al 2020 ; Viruez-Soto et al 2021 ; Zubieta-Calleja et al 2020 ). In our patients, serum EPO levels were not available, as EPO determinations are not part of any clinical laboratory routine, but an assumption of diminished levels would perfectly fit with their documented anemia prior to EPO treatment (Table 1 ).…”

Section: Discussionmentioning

confidence: 99%

Addressing the ‘hypoxia paradox’ in severe COVID-19: literature review and report of four cases treated with erythropoietin analogues

Begemann

Groß

Wincewicz

et al. 2021

Mol Med

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Background Since fall 2019, SARS-CoV-2 spread world-wide, causing a major pandemic with estimated ~ 220 million subjects affected as of September 2021. Severe COVID-19 is associated with multiple organ failure, particularly of lung and kidney, but also grave neuropsychiatric manifestations. Overall mortality reaches > 2%. Vaccine development has thrived in thus far unreached dimensions and will be one prerequisite to terminate the pandemic. Despite intensive research, however, few treatment options for modifying COVID-19 course/outcome have emerged since the pandemic outbreak. Additionally, the substantial threat of serious downstream sequelae, called ‘long COVID’ and ‘neuroCOVID’, becomes increasingly evident. Main body of the abstract Among candidates that were suggested but did not yet receive appropriate funding for clinical trials is recombinant human erythropoietin. Based on accumulating experimental and clinical evidence, erythropoietin is expected to (1) improve respiration/organ function, (2) counteract overshooting inflammation, (3) act sustainably neuroprotective/neuroregenerative. Recent counterintuitive findings of decreased serum erythropoietin levels in severe COVID-19 not only support a relative deficiency of erythropoietin in this condition, which can be therapeutically addressed, but also made us coin the term ‘hypoxia paradox’. As we review here, this paradox is likely due to uncoupling of physiological hypoxia signaling circuits, mediated by detrimental gene products of SARS-CoV-2 or unfavorable host responses, including microRNAs or dysfunctional mitochondria. Substitution of erythropoietin might overcome this ‘hypoxia paradox’ caused by deranged signaling and improve survival/functional status of COVID-19 patients and their long-term outcome. As supporting hints, embedded in this review, we present 4 male patients with severe COVID-19 and unfavorable prognosis, including predicted high lethality, who all profoundly improved upon treatment which included erythropoietin analogues. Short conclusion Substitution of EPO may—among other beneficial EPO effects in severe COVID-19—circumvent downstream consequences of the ‘hypoxia paradox’. A double-blind, placebo-controlled, randomized clinical trial for proof-of-concept is warranted.

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Decreased incidence, virus transmission capacity, and severity of COVID-19 at altitude on the American continent

Cited by 30 publications

References 31 publications

Diabetes increases the risk of COVID-19 in an altitude dependent manner: An analysis of 1,280,806 Mexican patients

Diabetes increases the risk of COVID-19 in an altitude dependent manner: An analysis of 1,280,806 Mexican patients

Elevated Humoral Immune Response to SARS-CoV-2 at High Altitudes Revealed by an Anti-RBD “In-House” ELISA

Addressing the ‘hypoxia paradox’ in severe COVID-19: literature review and report of four cases treated with erythropoietin analogues

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