Understanding the genetic etiology of COVID-19 requires a comprehensive understanding of the variant and haplotype landscape of all reported genomes of SARS-COV-2, the causative virus of the disease. Country-, state/region- and possibly even city-private variant profiles may contribute to varied disease exemplifications and fatality rates observed across the globe along with host factors such as age, ethnicity and comorbidity. The Children's Hospital of Los Angeles (CHLA) COVID-19 Analysis Research Database (CARD) captures up-to-date full-length SARS-CoV-2 sequences of ~50,500 isolates from GISAID, GenBank, CHLA Center for Personalized Medicine, and other sources (as of June 18, 2020). Among which, 49,637 isolates carry at least one variation from the reference genome NC_045512, a total of 6,070 variants and 2,513 haplotypes were detected in at least three isolates independently. Together, they constituted the most likely SARS-CoV-2 variant and haplotype landscapes world-wide currently. Evidence supporting positive (orf3a, orf8, S genes) and purifying (M gene) selections were detected, which warrants further investigation. Most interestingly, we identified 1,583 country-private variants from 10,238 isolates (20.6% overall) reported in 48 countries. 807 country-private haplotypes, defined as a haplotype shared by at least 5 isolates all of which came from the same country, were identified in in 8,656 isolates from 39 countries. United Kingdom, USA, and Australia had 464, 166 and 32 private haplotypes respectively, comprising 22.4%, 16.6% and 16.4% of the isolates from each country. Together with their descendent and private haplotypes with fewer members, 22,171 (45.8%) isolates carried country-private haplotypes globally. The percentage were 28.2-29.6% in January to March, and rapidly increased to 46.4% and 59.6% in April and May, co-occurring with global travel restrictions. The localization of the variant profiles appeared to be similarly accelerating from 14.2% in March and 28.4% in April to over 40% isolates carrying the country-private variants around May. In summary, a common pattern is seen world-wide in COVID-19 in which at the onset of disease there appeared to be a significant number of SARS-CoV-2 variants that accumulate quickly and then begin to rapidly coalesce into distinct haplotypes. This may be the result of localized outbreaks due to factors such as multiple points viral introduction, geographic separation and the introduction of policies such as travel restriction, social distancing and quarantine, resulting in the emergence of country-private haplotypes.

中文翻译：

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50,500个全球SARS-CoV-2分离株的综合变体和单倍型景观，并加速了国家/地区-私人变体图的积累

要了解COVID-19的遗传病因，就需要全面了解该疾病的致病性病毒SARS-COV-2的所有已报道基因组的变异和单倍型格局。国家，州/地区甚至城市私有的变异情况可能会导致在全球范围内观察到各种疾病例证和致死率，以及诸如年龄，种族和合并症等宿主因素。洛杉矶儿童医院（CHLA）COVID-19分析研究数据库（CARD）捕获了来自GISAID，GenBank，CHLA个性化医学中心和其他机构的约50,500个分离株的最新SARS-CoV-2全长序列来源（截至2020年6月18日）。其中49637株带有参考基因组NC_045512的至少一个变异，共有6070个变异，而2个 在至少三个分离株中独立检测出513个单倍型。它们共同构成了目前全球最有可能的SARS-CoV-2变异和单倍型景观。检测到支持阳性（orf3a，orf8，S基因）和纯化（M基因）选择的证据，值得进一步研究。最有趣的是，我们从48个国家/地区的10238个分离物中分离出1583个国家/地区的变体（总体占20.6％）。在来自39个国家/地区的8656个分离物中鉴定出807个国家/地区的私有单倍型，定义为至少5个分离物共有的同一型。英国，美国和澳大利亚分别拥有464、166和32个私人单倍型，分别占每个国家/地区的22.4％，16.6％和16.4％。再加上成员较少的后代和私人单倍型，全球共有22,171（45.8％）个分离株携带国别-单倍型。1月至3月，这一比例为28.2-29.6％，4月和5月迅速增加至46.4％和59.6％，这是全球旅行限制的共同原因。变异体谱的本地化似乎从3月的14.2％和4月的28.4％加速到5月前后携带国别变异体的40％以上的分离株。总而言之，在世界范围内都可以看到一种常见的COVID-19模式，其中在疾病发作时似乎有大量的SARS-CoV-2变异体迅速积累，然后迅速融合为不同的单倍型。这可能是由于多种因素引起的局部爆发，例如病毒多点传播，地域分离以及政策出台（例如旅行限制，