Impact of altitude on COVID-19 aggregation infection in China: evidence from linkage of environmental factors, COVID-19, and genome diversity (Preprint)
Zhuoga Deji, Yuantao Tong, Zeyu Zhang, Meng Fang, James C Crabble, Ying Wang, Xiaoyan Zhang
doi:10.2196/preprints.43585
Background: The novel coronavirus disease due to SARS-Cov-2 (COVID-19) has been declared as a global pandemic and is still ongoing worldwide. While based on the government report and genome diversity study, the overall COVID-19 mortality and infection cases are significantly low in high altitude place. Several factors which may effect the development tendency of COVID-19 were investigated. However, there is limited information on the evidence of low infection cases in altitude area, and how underlying biological mechanism effect the aggregation infection of COVID-19 in altitude area of China. Objective: This study is aiming to investigate the impacts of altitude on COVID-19 aggregation infection in China by analyzing the correlation between environmental factors with COVID-19 confirmed cases and viral mutations.
Methods: We first examined the correlation between altitude and COVID-19 infection through linear regression, and further identified several major factors correlated to COVID-19 through text mining in the zero-shot model. Spearman correlation was conducted to analyze the correlation between selected meteorological factors and air quality with COVID-19 confirmed cases in high altitude regions of China. We further identified different virus mutations at both high and low altitudes, and the relationship between our environmental factors and mutation frequency using the same correlation technique.
Results: The linear regression analysis revealed a negative correlation between altitude and COVID-19 confirmed case in China. The Spearman correlation analysis indicated that the average temperature, sun hours, UV index, wind speed and average concentration of NO2 were negatively correlated to daily new confirmed cases at high altitude regions in China, while air pressure, average concentration of PM2.5 were positively correlated. Further research of mutation diversity in low-and highaltitude groups showed lower genetic diversity among nucleotides for each SARS-CoV-2 genome (p < .001) and three open reading frames (ORFs) (p < .001) compared to 300 sequences of low altitude. Further correlation analysis investigated positive correlations between altitude, wind speed, atmospheric pressure with some key nonsynonymous mutations, and negative correlation with temperature, UV index, sun hours.
Conclusions: The characteristics of environmental factors including meteorology and air quality parameters largely reflect the evidence of low COVID-19 confirmed cases in high altitude region of China. Besides, environmental factors on virus mutation also adds knowledge of altitude impact on aggregation infection of COVID-19 and provides novel suggestions for preventive intervention.
test was used to evaluate the significance of mutation frequency in each of the ORFs (Figure 5A ). The amino acid mutation frequency values for the three ORFs known as ORF1b, ORF7a, and ORF7b were significantly lower in the high-altitude group than in the low-altitude group (p < .001), but higher for the S and N genes (p < .001). Among these, differences between high-and low-altitude groups showed 44 nonsynonymous mutations and 32 synonymous mutations (Figure 5B
Correlation analysis between mutation frequency and environmental factors The impact of 7 environmental factors on nonsynonymous mutation frequency was analyzed through all sequences (Figure 6 and Multimedia Appendix 8). Most of the nonsynonymous mutations had a positive correlation with altitude, wind speed, and atmospheric pressure, whereas UV index, relative humidity, and sun hour (p < .01 or p < .05) showed a negative correlation. The highest correlation between mutation frequency and environmental factors was found for altitude with N_G29427A, ORF1b_C20320T, and ORF1a _C1191T (r = 0.53, p < .001), followed by UV index with ORF8_C28093T, S_A23063T (r = -0.42, p < .001), and temperature with ORF8_C28093T, S_C23604A, S_A23063T, ORF1a_G6671A. Some significant nonsynonymous
Conflicts of Interest The authors disclose no conflicts of interest.
Author's Contributions
References
Arias-Reyes, Zubieta-Deurioste, Poma-Machicao, Aliaga-Raduan, Carvajal-Rodriguez et al., Does the pathogenesis of SARS-CoV-2 virus decrease at high-altitude? Respiratory physiology & neurobiology,
doi:10.1016/j.resp.2020.103443Bashir, Ma, Bilal, Komal, Bashir et al., Correlation between climate indicators and COVID-19 pandemic in New York, USA, The Science of the total environment,
doi:10.1016/j.scitotenv.2020.138835Bhadra, Mukherjee, Sarkar, Impact of population density on Covid-19 infected and mortality rate in India, Modeling earth systems and environment,
doi:10.1007/s40808-020-00984-7Cano-Pérez, Torres-Pacheco, Mc, García-Díaz, Montalvo-Varela et al., Negative Correlation between Altitude and COVID-19 Pandemic in Colombia: A Preliminary Report, The American journal of tropical medicine and hygiene,
doi:10.4269/ajtmh.20-1027Carleton, Cornetet, Huybers, Meng, Proctor, Global evidence for ultraviolet radiation decreasing COVID-19 growth rates, Proceedings of the National Academy of Sciences of the United States of America,
doi:10.1073/pnas.2012370118Chen, Qin, Wu, Xu, Gao et al., Clinical characteristics and laboratory features of COVID-19 in high altitude areas: A retrospective cohort study, PloS one,
doi:10.1371/journal.pone.0249964Dyer, China stops counting cases as models predict a million or more deaths, BMJ (Clinical research,
doi:10.1136/bmj.p2Fiasca, Minelli, Maio, Minelli, Vergallo et al., Associations between COVID-19 Incidence Rates and the Exposure to PM2.5 and NO(2): A Nationwide Observational Study in Italy, International journal of environmental research and public health,
doi:10.3390/ijerph17249318Ganasegeran, Jamil, Ch'ng, Looi, Peariasamy, Influence of Population Density for COVID-19 Spread in Malaysia: An Ecological Study, International journal of environmental research and public health,
doi:10.3390/ijerph18189866Hakami, Dobie, Studying the effect of particulate matter as SARS-CoV-2 transmitters, Journal of public health research,
doi:10.4081/jphr.2021.2521Hao, Li, Hao, Zhao, Wan et al., Global Evidence of Temperature Acclimation of COVID-19 D614G Linage, Global challenges,
doi:10.1002/gch2.202000132Isaia, Diémoz, Maluta, Fountoulakis, Ceccon et al., Does solar ultraviolet radiation play a role in COVID-19 infection and deaths? An environmental ecological study in Italy, The Science of the total environment,
doi:10.1016/j.scitotenv.2020.143757Ismail, Jalaludin, Bakar, Hisamuddin, Nfjajoae, Association of Traffic-Related Air Pollution (TRAP) with DNA Damage and Respiratory Health Symptoms among Primary School Children in Selangor
Li, Xu, Dai, Huang, Ma et al., Air pollution and temperature are associated with increased COVID-19 incidence: A time series study, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases,
doi:10.1016/j.ijid.2020.05.076Mengist, Kombe, Mekonnen, Abebaw, Getachew, Mutations of SARS-CoV-2 spike protein: Implications on immune evasion and vaccine-induced immunity, Seminars in immunology,
doi:10.1016/j.smim.2021.101533Mustafa, Kalbacher, Burster, Occurrence of a novel cleavage site for cathepsin G adjacent to the polybasic sequence within the proteolytically sensitive activation loop of the SARS-CoV-2 Omicron variant: The amino acid substitution N679K and P681H of the spike protein, PloS one,
doi:10.1371/journal.pone.0264723Ortiz-Prado, Simbaña-Rivera, Fernandez-Naranjo, Vásconez, Henriquez-Trujillo et al., SARS-CoV-2 Viral Load Analysis at Low and High Altitude: A Case Study from Ecuador, International journal of environmental research and public health,
doi:10.3390/ijerph19137945Pani, Lin, Ravindrababu, Association of COVID-19 pandemic with meteorological parameters over Singapore, The Science of the total environment,
doi:10.1016/j.scitotenv.2020.140112Pansini, Djm, Higher virulence of COVID-19 in the air-polluted regions of eight severely affected countries
Pansini, Fornacca, COVID-19 Higher Mortality in Chinese Regions With Chronic Exposure to Lower Air Quality, Frontiers in public health,
doi:10.3389/fpubh.2020.597753Pirouz, Haghshenas, Pirouz, Haghshenas, Piro, Development of an Assessment Method for Investigating the Impact of Climate and Urban Parameters in Confirmed Cases of COVID-19: A New Challenge in Sustainable Development, International journal of environmental research and public health,
doi:10.3390/ijerph17082801Ramesh, Govindarajulu, Parise, Neel, Shankar et al., Emerging SARS-CoV-2 Variants: A Review of Its Mutations, Its Implications and Vaccine Efficacy, Vaccines,
doi:10.3390/vaccines9101195Ratnesar-Shumate, Williams, Green, Krause, Holland et al., Simulated Sunlight Rapidly Inactivates SARS-CoV-2 on Surfaces, The Journal of infectious diseases,
doi:10.1093/infdis/jiaa274Rocklöv, Sjödin, High population densities catalyse the spread of COVID-19, Journal of travel medicine,
doi:10.1093/jtm/taaa038Segovia-Juarez, Castagnetto, Gonzales, High altitude reduces infection rate of COVID-19 but not case-fatality rate, Respiratory physiology & neurobiology,
doi:10.1016/j.resp.2020.103494Sharif, Dey, Impact of population density and weather on COVID-19 pandemic and SARS-CoV-2 mutation frequency in Bangladesh, Epidemiology and infection,
doi:10.1017/s0950268821000029Sharif, Sarkar, Ahmed, Ferdous, Nobel et al., Environmental correlation and epidemiologic analysis of COVID-19 pandemic in ten regions in five continents, Heliyon,
doi:10.1016/j.heliyon.2021.e06576Sivasubramanian, Gopalan, Ramesh, Padmanabhan, Mone et al., Phylodynamic Pattern of Genetic Clusters, Paradigm Shift on Spatio-Temporal Distribution of Clades, and Impact of Spike Glycoprotein Mutations of SARS-CoV-2 Isolates from India, Journal of global infectious diseases,
doi:10.4103/jgid.jgid_97_21Song, Han, Feng, Hui, Zhou et al., High altitude Relieves transmission risks of COVID-19 through meteorological and environmental factors: Evidence from China, Environmental research,
doi:10.1016/j.envres.2022.113214Srivastava, Garg, Bansal, Kumar, SARS-CoV-2 infection: physiological and environmental gift factors at high altitude, Virusdisease,
doi:10.1007/s13337-020-00626-7Stephens, Chernyavskiy, Bruns, Impact of altitude on COVID-19 infection and death in the United States: A modeling and observational study, PloS one,
doi:10.1371/journal.pone.0245055Sun, Gu, Cao, Chen, Ye et al., Characterization and structural basis of a lethal mouse-adapted SARS-CoV-2, Nature communications,
doi:10.1038/s41467-021-25903-xSun, Zhang, Yang, Wan, Wang, Impacts of geographic factors and population density on the COVID-19 spreading under the lockdown policies of China, The Science of the total environment,
doi:10.1016/j.scitotenv.2020.141347Tong, Tan, Huang, Zhang, Zong et al., ViMRT: a text-mining tool and search engine for automated virus mutation recognition, Bioinformatics,
doi:10.1093/bioinformatics/btac721Ujiie, Tsuzuki, Ohmagari, Effect of temperature on the infectivity of COVID-19, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases,
doi:10.1016/j.ijid.2020.04.068Wu, Jmjj, Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control, Prevention
Yang, Yu, Chang, Hsu, D614G mutation in the SARS-CoV-2 spike protein enhances viral fitness by desensitizing it to temperature-dependent denaturation, The Journal of biological chemistry,
doi:10.1016/j.jbc.2021.101238Yao, Pan, Liu, Meng, Wang et al., No association of COVID-19 transmission with temperature or UV radiation in Chinese cities, The European respiratory journal,
doi:10.1183/13993003.00517-2020Zagordi, Däumer, Beisel, Beerenwinkel, Read length versus depth of coverage for viral quasispecies reconstruction
Zhang, Fang, Wu, Zong, Huang et al., Large-Scale Biomedical Relation Extraction Across Diverse Relation Types: Model Development and Usability Study on COVID-19, Journal of medical Internet research,
doi:10.2196/48115Zhu, Xie, Huang, Ljsotte, Association between short-term exposure to air pollution and COVID-19 infection: Evidence from China
