严重急性呼吸综合症冠状病毒2变异株
本文主要讲述严重急性呼吸综合征冠状病毒2变异株及其发生的错义突变。
引发2019冠状病毒病的严重急性呼吸系统综合征冠状病毒2(SARS-CoV-2冠状病毒)容易发生突变而产生变异株,关键病毒蛋白的突变即可能意味着其出现,目前已有多个变异株在世界各地形成并传播。由于病毒的核酸序列变异有可能导致抗原漂移,而使得病毒得以逃避宿主的免疫应答,并影响疫苗的效力[1],这种现象称为免疫逃避。
已有五种被世界卫生组织认定为值得关注的变异株,它们分别为阿尔法变异株、贝塔变异株、伽马变异株、德尔塔变异株以及奥密克戎变异株。
变异株对照表
编辑最初检出 | 代号 | 重要突变 | 传播 | 相对于武汉首次发现变体的临床变化 | ||||||
---|---|---|---|---|---|---|---|---|---|---|
地区 | 日期 | WHO标签[2] | PANGO谱系 | PHE变种[3] | Nextstrain分化枝 | 传播力 | 致命性 | 抗原性 | ||
尼日利亚 | 2020年8月[4] | — | B.1.1.207 | — | — | P681H[5] | 多国[6] | 无变化[5] | 无变化[5] | |
英国 | 2020年9月[2][7] | 阿尔法[A] | B.1.1.7[8] | VOC-20DEC-01 | 20I (V1)[9] | N501Y, 69–70del, P681H[5][10][11][12] | 全球[7] | 增高≈ ( 82%– 43 130%) [13] | 正在调查 | 抗体中和效力略降低[14] |
2021年1月[3] | B.1.1.7#E484K[3] | VOC-21FEB-02 | 20I (V1) | N501Y, 69–70del, P681H,[5][15] E484K | 多国 | 正在调查 | 正在调查 | 正在调查 | ||
丹麦 | 2020年9月[16] | — | B.1.1.298[17] | — | — | Y453F, 69–70deltaHV[18] | 可能灭绝[19] | |||
南非 | 2020年5月[2] | 贝塔[A] | B.1.351[5][8] | VOC-20DEC-02 | 20H (V2)[20] | N501Y, K417N, E484K[5][21][22][23][24][25] | 多国[26] | 增高≈ ( 50%– 20 113%) | 无变化[27] | 显著降低抗体中和效力 |
日本 巴西 |
2020年11月[2] | 伽马[A] | P.1谱系[10][8] | VOC-21JAN-02 | 20J (V3)[31] | N501Y, E484K, K417T[5][32][33][34] | 美国、巴西等68国[35] | 增高≈ ( 161%– 145 174%) |
致命性增高≈ ( 50%– 20 90%) |
抗体中和效力降低 |
印度 | 2020年10月[2] | 德尔塔[A] | B.1.617.2[39] | VOC-21APR-02 | 21A[40] | T478K, L452R, P681R | 多国 | 增高≈ 198% |
正在调查[F] | 抗体中和效力降低[46][30] |
美国 | 2020年3月[2][47] | 艾普西隆 | B.1.427,B.1.429[47][48] | — | 21C[49] | L452R[48] | 多国[48] | 增高≈ ( 20%) 18.6%–24.2% |
恢复期和疫苗接种后血清中和效力降低 | |
巴西 | 2020年4月[51] | 泽塔 | P.2 | VUI-21JAN-01 | 20B/S.484K[52] | E484K,D614G,V1176F[53] | 多国[51] | 单克隆抗体中和效力可能降低,疫苗接种后血清中和效力降低 | ||
英国 尼日利亚 |
2020年12月[2][54] | 埃塔 | B.1.525[55] | VUI-21FEB-03 | 21D[56] | E484K, F888L[55] | 加拿大、美国、德国等69国[54] | 单克隆抗体、恢复期和疫苗接种后血清中和效力可能降低 | ||
菲律宾 | 2021年1月[2] | 西塔 | P.3[57] | VUI-21MAR-02 | 21E[58] | E484K,N501Y,P681H,141–143del[59] | 菲律宾、美国等17国[57] | |||
印度 | 2020年10月[2] | 卡帕 | B.1.617.1[39] | VUI-21APR-01 | 21B[60] | E484Q, L452R, P681R[61] | 多国 | 抗体中和效力降低[46] | ||
秘鲁 | 2020年8月[62] | 拉姆达 | C.37[63] | VUI-21JUN-01 | 21G[64] | G75V,T76I,247-253del,L452Q,F490S,D614G,T859N[65] | 智利、美国、秘鲁等44国[63] | |||
哥伦比亚 | 2021年1月 | 缪 | B.1.621 | VUI-21JUL-1 | 21H | T95I、Y144S、Y145N、R346K、E484K N501Y、D614G、P681H、D950N |
哥伦比亚、美国等60国 | |||
博茨瓦纳 | 2021年11月 | 奥密克戎[A] | B.1.1.529 | VUI-21NOV-1 | 21K | A67V、Δ69-70、T95I、G142D、Δ143-145、Δ211 L212I、ins214EPE、G339D、S371L、S373P、S375F K417N、N440K、G446S、S477N、T478K、E484A Q493K、G496S、Q498R、N501Y、Y505H、T547K D614G、H655Y、N679K、P681H、N764K |
博茨瓦纳、南非等数国 | 有可能提高[66] | 相对于 德尔塔: ( −63%– 69 74%) [67] | 疫苗对有症状疾病的免疫效果降低 |
- ^ 1.0 1.1 1.2 1.3 1.4 被世界卫生组织列为高关注变异株
- ^ 2.0 2.1 The reported confidence or credible interval has a low probability, so the estimated value can only be understood as possible, not certain nor likely.
- ^ Another study[37] has estimated that P.1 may be ≈ (50% CrI, 100%– 70) more transmissible. 140%[B]
- ^ Preliminary results from a study in the Southern Region of Brazil found P.1 much more lethal for healthy young people. In groups without pre-existing conditions, the variant was found to be ≈ ( 490%– 220 985%) more lethal for men in the 20-39 age group, ≈ ( 465%– 190 1003%) more lethal for women in the 20-39 age group and ≈ ( 670%– 401 1083%) for women in the 40-59 age group.[38]
- ^ About ( 64%– 26 113%) more transmissible than the 阿尔法 variant,[41] so 1.64 × 1.82 ≈ 2.98.
- ^ 相对2020年初参考病毒株,德尔塔变异株症状发展更快、更严重[42];相对阿尔法变异株,感染者住院率增加约一倍[43][44]。但根据英格兰公共卫生署6月份报告,德尔塔变异株病例死亡率累计0.2%(如只计无注射疫苗则0.13%),而旧有阿尔法变异株则为1.9%[45]
命名法
编辑目前严重急性呼吸系统综合征冠状病毒2之变异株有三个常用的命名系统,分别由GISAID、Nextstrain和PANGO建立。[2]
2021年5月31日,世界卫生组织宣布为重要变种病毒提供希腊字母标签,为免首先发现变种病毒的国家遭受歧视及污名化。[68]其中,命名规则在缪变异株后跳过了希腊字母“Nu”和“Xi”这两个字母。据俄罗斯官方电视台《RT》报导,有不具名的WHO官员透露跳过“Nu”是为避免与发音相同的“New”混淆,至于跳过“Xi”则是由于这个字母的姓氏很普遍,为了避免“对区域的污名化”[69][70][71][72]。
支序演化树
编辑以下为严重急性呼吸系统综合征冠状病毒2主要变种的支序演化树简化示意图。[75]
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关注度之基准
编辑现阶段的主流变异株
编辑需要关注的变异株(VOC)
编辑病毒变异是一个自然随机过程,并引发关切的程度取决于其导致的传染性、发病率、死亡率,及逃避检测、免疫与治疗的风险。目前在世界的主要变异株为最早发现于非洲南部由希腊字母“奥密克戎”标记。
奥密克戎(B.1.1.529谱系)
编辑B.1.1.529变异株(WHO命名为奥密克戎[109][110][111])是目前变异最多的2019冠状病毒病病毒。据媒体简报会上发布:这个变异株有超过50个突变[112],而单单在刺突蛋白的突变也有32种[110][113][112]。
- 于2021年11月,在非洲南部的博茨瓦纳和南非发现[112][114][111]。
- 2021年11月24日,升级为“VUM”等级。
- 2021年11月26日,再升级为“VOC”等级。
- 目前变种分支亚型:BA.1(标准亚型)、BA.2、BA.3、BA.4、BA.5,总共超过千种以上的“次分支”、“子代”及“重组”变异株。
目前“VOC-VOI”等级(需要留意)变异株
编辑- BA.2.86:被称为“皮罗拉”(Pirola)
- JN.1
目前“VOC-VUM”等级(监视)变异株
编辑- KP.2
- KP.3
- KP.3.1.1
- JN.1.7
- JN.1.18
- LB.1
- XEC
过去的主流变异株
编辑需要关注的变异株(Previous VOC)
编辑阿尔法(B.1.1.7谱系)
编辑B.1.1.7谱系,WHO命名为“阿尔法”,又称VOC 202012/01,并称501Y.V1变种。部分与“N501Y”突变有关。有23个病毒基因变异点。
- 在2020年9月,首次从英国东南方的肯特郡(Kent)所发现采集的样本中发现[115]。
- 2020年12月18日,升级为“VOC”等级。
- 2022年3月9日,降级为“Previous VOC”等级。
贝塔(B.1.351谱系)
编辑B.1.351谱系,WHO命名为“贝塔”,又称501Y.V2变种。与“N501Y”、“K417N”、“E484K”突变有关,与先前的新冠病毒变种相比,501Y.V2变种的传染率增加约50%。[116]有证据表明,501Y.V2变种的刺突蛋白突变E484K可能会影响一些多克隆抗体和单克隆抗体的中和作用。当前尚未有证据表明该变种影响2019冠状病毒病的严重程度[117]。。
- 2020年5月,在南非东开普省的纳尔逊·曼德拉湾发现。
- 2020年12月18日,被南非科学家和卫生官员报道。[118][119]
- 2020年12月18日,升级为“VOC”等级。
- 2022年3月9日,降级为“Previous VOC”等级。
伽马(P.1谱系)
编辑P.1谱系,WHO命名为“伽马”,又称501Y.V3变种。包括三个相关突变:“N501Y”、“E484K”和“K417T”。
- 2020年11月,在巴西发现。
- 2021年1月2日,在东京国际机场从四名巴西飞抵日本的旅客发现,由日本国立感染症研究所报道[117]。
- 2021年1月11日,升级为“VOC”等级。
- 2022年3月9日,降级为“Previous VOC”等级。
德尔塔(B.1.617.2谱系)
编辑B.1.617谱系是2020年10月于印度发现的一种双突变变异株。直到2021年1月前,该变异株的感染人数都寥寥无几。4月时该变异株已经蔓延至超过20个国家,遍及南极洲和南美洲以外的所有大洲。[120][121][122]
在该变异株约15个谱系定义突变中包括刺突蛋白突变D111D(同义突变)、G142D[123]、P681R、E484Q[107]、L452R[124],其中后两个突变可能会影响恢复期血浆和单克隆抗体的中和作用。[125]
英国公共卫生部于5月7日将B.1.617.2列为“高关注变异株”,命名为VOC-21APR-02。[96][126]
5月10日WHO称,因为B.1.617较高的传染性,该变异正被列为全球范围内受关切变种[127]。6月1日WHO将受关切变种限定为B.1.617谱系当中的B.1.617.2(德尔塔)变种。[128] 稍后WHO将B.1.617.2命名为“德尔塔”。
5月21日,越南宣布发现一种传播性更高,由德尔塔变异株加上阿尔法变异株上突变的病毒株。[129]6月3日,WHO澄清该病毒株不符合新混合变种的定义,并将其列为带有突变的德尔塔变种。[130]
据报道,德尔塔变异株基本传染数R0大约为6(有说法称其高达8或9)[131],是严重急性呼吸系统综合征冠状病毒2原始毒株基本传染数的2倍以上。[132]
- 2021年4月4日,为升级为“VOI”等级。
- 2021年5月11日,为升级为“VOC”等级。
- 2022年6月7日,降级为“Previous VOC”等级。
需要留意的变异株(Previous VOI)
编辑艾普西隆(B.1.427谱系、B.1.429谱系)
编辑B.1.427谱系、B.1.429谱系,WHO命名为“艾普西隆”,于2020年3月在美国加州首次发现。
- 2021年3月5日,升级为“VOI”等级。
- 2021年7月6日,降级为“Previous VOI”等级。
泽塔(P.2谱系)
编辑P.2谱系,WHO命名为“泽塔”,于2020年4月在巴西里约热内卢首次发现。
- 2021年3月17日,升级为“VOI”等级。
- 2021年7月6日,降级为“Previous VOI”等级。
埃塔(B.1.525谱系)
编辑B.1.525谱系,WHO命名为“埃塔”,于2020年12月在尼日利亚首次发现。
- 2021年3月17日,升级为“VOI”等级。
- 2021年9月20日,降级为“Previous VOI”等级。
约塔(B.1.526谱系)
编辑B.1.526谱系,WHO命名为“约塔”,于2020年11月在美国纽约首次发现。
- 2021年3月20日,升级为“VOI”等级。
- 2021年9月20日,降级为“Previous VOI”等级。
西塔(P.3谱系)
编辑P.3谱系,WHO命名为“西塔”,于2021年1月在菲律宾首次发现。
- 2021年3月24日,升级为“VOI”等级。
- 2021年7月6日,降级为“Previous VOI”等级。
卡帕(B.1.617.1)
编辑B.1.617谱系的三个子谱系之一当中的“B.1.617.1”,WHO命名为“卡帕”,于2020年10月在印度首次发现。
- 2021年4月4日,升级为“VOI”等级。
- 2021年9月20日,降级为“Previous VOI”等级。
拉姆达(C.37谱系)
编辑C.37谱系,WHO命名为“拉姆达”,于2020年8月在秘鲁首次发现。
- 2021年6月14日,升级为“VOI”等级。
- 2022年3月9日,降级为“Previous VOI”等级。
缪(B.1.621谱系)
编辑B.1.621谱系,WHO命名为“缪”,于2021年1月在哥伦比亚首次发现。
- 2021年8月30日,升级为“VOI”等级。
- 2022年3月9日,降级为“Previous VOI”等级。
备注
编辑- ^ 台湾疾管署按美国CDC定义分三类,称为:需留意变异株(Variants of Interest, VOI)、高关注变异株(Variants of Concern, VOC)、高冲击变异株(Variant of High Consequence)。
参见
编辑参考文献
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Sekventeringen af de positive prøver viser samtidig, at der ikke er påvist yderligere tilfælde af minkvariant med cluster 5 siden den 15. september, hvorfor Statens Serums Institut vurderer, at denne variant med stor sandsynlighed er døet ud. ("With high probability [...] died out")
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I should note here that there's another strain in South Africa that is bringing on similar concerns. This one has eight mutations in the Spike protein, with three of them (K417N, E484K and N501Y) that may have some functional role.
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The new variant was found to be about 2.6 times more transmissible (95% Confidence Interval (CI): 2.4–2.8) than previous circulating variant(s). ... Table 1: Summary of the fitted parameters and respective confidence intervals considering the entire period, November 1 2020-January 31, 2021 maintaining the same pathogenicity of the previous variant. Parameter: Relative transmission rate for the new variant. Estimate: 2.61. 2.5%: 2.45. 97.5%: 2.76.
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Within this plausible region of parameter space, P.1 can be between 1.7 and 2.4 times more transmissible (50% BCI, 2.0 median, with a 99% posterior probability of being >1) than local non-P1 lineages and can evade 21 to 46% (50% BCI, 32% median, with a 95% posterior probability of being able to evade at least 10%) of protective immunity elicited by previous infection with non-P.1 lineages, corresponding to 54 to 79% (50% BCI, 68% median) cross-immunity ... We estimate that infections are 1.2 to 1.9 times more likely (50% BCI, median 1.5, 90% posterior probability of being >1) to result in mortality in the period after the emergence of P.1, compared with before, although posterior estimates of this relative risk are also correlated with inferred cross-immunity. More broadly, the recent epidemic in Manaus has strained the city’s health care system, leading to inadequate access to medical care. We therefore cannot determine whether the estimated increase in relative mortality risk is due to P.1 infection, stresses on the Manaus health care system, or both. Detailed clinical investigations of P.1 infections are needed.
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Female 20 to 39 years old, with no pre-existing risk conditions, were at risk of death 5.65 times higher in February (95% CI, 2.9-11.03; p <0.0001) and in the age group of 40 and 59 years old, this risk was 7.7 times higher (95% CI, 5.01-11.83; p <0.0001) comparing with November-December. ... The heterogeneity observed between the age groups was greater when we analyzed the subgroup of the population without preexisting risk conditions where we found that the CFR in the female sex in the second wave was 1.95 times (95% CI, 1.38-2.76) the CFR of the first wave in the population over 85 years old and was 7.7 times (95% CI, 5.01-11.83; p < 0.0001) in the population between 40 and 59 years old. In the male population without previous diseases, the CFR in the second wave was 2.18 (95% CI, 1.62-2.93) times the CFR of the first wave in the population over 85 years old and 5.9 (95% CI, 3.2-10.85; p < 0, 0001) higher in the range between 20 and 39 years old.
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外部链接
编辑- WHO: Tracking SARS-CoV-2 variants (页面存档备份,存于互联网档案馆)
- Science Brief: Emerging SARS-CoV-2 Variants (CDC) (页面存档备份,存于互联网档案馆)
- SARS-CoV-2 Variant Classifications and Definitions (CDC) (页面存档备份,存于互联网档案馆)
- Variants of concern or under investigation: data up to 5 May 2021 (PHE) (页面存档备份,存于互联网档案馆)
- SARS-CoV-2 variants of concern as of 11 May 2021 (ECDC) (页面存档备份,存于互联网档案馆)
- Living Evidence - SARS-CoV-2 variants (页面存档备份,存于互联网档案馆)
- Coronavirus Variants and 缪tations (页面存档备份,存于互联网档案馆)