严重急性呼吸综合症冠状病毒2变异株

SARS-CoV-2突變所產生之變異株
(重定向自武肺變種

本文主要讲述严重急性呼吸综合症冠状病毒2变异株及其发生的错义突变

引发2019冠状病毒病严重急性呼吸综合征冠状病毒2(SARS-CoV-2冠状病毒)容易发生突变而产生變異株英语Variant (biology),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免疫应答,并影响疫苗的效力[1],这种现象称为免疫逃避英语antigenic escape

已有五种被世界卫生组织認定为值得关注的变异株,它們分別為Alpha變異株Beta變異株Gamma變異株Delta變異株以及Omicron變異株

變異株對照表

最初檢出 代號 重要突变 传播 相对于武汉首次发现变体的临床变化
地區 日期 WHO标签[2] PANGO谱系 PHE英语Public Health England变种[3] Nextstrain英语Nextstrain分化枝 传播力 致命性 抗原性
  奈及利亞 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] Alpha[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% (43130%) [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書面挪威語Lineage B.1.1.7 with E484K[3] VOC-21FEB-02 20I (V1) N501Y, 69–70del, P681H,[5][15] E484K 多國 正在调查 正在调查 正在调查
  丹麦 2020年9月[16] B.1.1.298英语Cluster 5[17] Y453F, 69–70deltaHV[18] 可能灭绝[19]
  南非 2020年5月[2] Beta[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% (20113%) 无变化[27] 显著降低抗体中和效力[28][29][14][30]
  日本
  巴西
2020年11月[2] Gamma[A] P.1譜系[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% (145174%)[36][C] 致命性增高≈50% (2090%) [37][B][D] 抗体中和效力降低[10]
  印度 2020年10月[2] Delta[A] B.1.617.2[39] VOC-21APR-02 21A[40] T478K, L452R, P681R 多国 增高≈198%[E] 正在调查[F] 抗体中和效力降低[46][30]
  美国 2020年3月[2][47] Epsilon B.1.427,B.1.429[47][48] 21C[49] L452R[48] 多国[48] 增高≈20% (18.6%–24.2%)[50] 恢复期和疫苗接种后血清中和效力降低
  巴西 2020年4月[51] Zeta 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
  奈及利亞
2020年12月[2][54] Eta 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
  菲律賓 2021年1月[2] Theta 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] Kappa 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]
  秘魯 2020年8月[62] Lambda C.37[63] VUI-21JUN-01 21G[64] G75V,T76I,247-253del,L452Q,F490S,D614G,T859N[65] 智利、美国、祕魯等44國[63]
  哥伦比亚 2021年1月 Mu B.1.621 VUI-21JUL-1 21H T95I、Y144S、Y145N、R346K、E484K
N501Y、D614G、P681H、D950N
哥倫比亞、美國等60國
  博茨瓦纳 2021年11月 Omicron[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 Delta:−63% (6974%) [67] 疫苗对有症状疾病的免疫效果降低[66]
  1. ^ 1.0 1.1 1.2 1.3 1.4 被世界卫生组织列为高關注變異株英语Variant of concern
  2. ^ 2.0 2.1 The reported confidence or credible interval英语credible interval has a low probability, so the estimated value can only be understood as possible, not certain nor likely.
  3. ^ Another study[37] has estimated that P.1 may be ≈100% (50% CrI, 70140%) more transmissible.[B]
  4. ^ 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% (220985%) more lethal for men in the 20-39 age group, ≈465% (1901003%) more lethal for women in the 20-39 age group and ≈670% (4011083%) for women in the 40-59 age group.[38]
  5. ^ About 64% (26113%) more transmissible than the Alpha variant,[41] so 1.64 × 1.82 ≈ 2.98.
  6. ^ 相对2020年初参考病毒株,Delta變異株症状发展更快、更严重[42];相對Alpha變異株,感染者住院率增加约一倍[43][44]。但根據英格蘭公共衛生署6月份報告,Delta變異株病例死亡率累計0.2%(如只計無注射疫苗則0.13%),而舊有Alpha變異株則為1.9%[45]

命名法

目前严重急性呼吸综合征冠状病毒2之變異株有三个常用的命名系统,分别由GISAIDNextstrain英语NextstrainPANGO建立。[2]

2021年5月31日,世界卫生组织宣布为重要變種病毒提供希臘字母标签,為免首先發現變種病毒的國家遭受歧視汙名化[68]其中,命名規則在Mu變異株後跳過了希臘字母「Nu」和「Xi」這兩個字母。據俄羅斯官方電視台《RT》報導,有不具名的WHO官員透露跳過「Nu」是為避免與發音相同的「New」混淆,至於跳過「Xi」則是由於這個字母的姓氏很普遍,為了避免「對區域的汙名化」[69][70][71][72]

支序演化树

 
PANGO命名系统的SARS-CoV-2谱系图
 
随疫情发展,D614G变异英语Variants of SARS-CoV-2#D614G(属B.1演化支[73])逐渐成为目前全球主要传播的严重急性呼吸综合征冠状病毒2类型。[74]

以下为严重急性呼吸综合征冠状病毒2主要变种的支序演化树简化示意图。[75]

SARS-CoV-2
A.1–A.6

WIV04/2019(参考基因组[76]

B.1[74]
B.1.1[94]
B.1.1.1
C.1

C.1.2 (B.1.1.1.1.2)[73][77]

C.36書面挪威語C.36 (B.1.1.1.36)[73]

Lambda變異株 (C.37谱系, B.1.1.1.37) [62][78][73]

Alpha變異株(B.1.1.7谱系) [A]

VOC-21FEB-02 (B.1.1.7#E484K)書面挪威語Lineage B.1.1.7 with E484K [3][A]

B.1.1.28

Gamma變異株 (P.1谱系) [A]

P.2谱系英语SARS-CoV-2 Zeta variant (Zeta) [79]

P.3谱系英语SARS-CoV-2 Theta variant (Theta)

B.1.1.207書面挪威語Lineage B.1.1.207

B.1.1.318 (AZ.1 - AZ.5)[73][80]

Omicron變異株(B.1.1.529谱系)[95][73][87][A]

BA.1[81]

BA.2[81]

BA.2.12 (BA.2.12.1)[82][83]

BA.2.75

BA.2.75.2 [84][85][86]

XBB (与 BA2.10.1 重组而形成) [87][88][89]

CH.1.1 [90]

BA.2.86
→ JN.1

KP.2

KP.3

LB.1

BA.3[87]

BA.4[87]

BA.4.6 [87][91][92]

BA.5

BA.5.1[87]

BA.5.2 (BF.7, BA.5.2.1.7) [87][93]

BA.5.3 (BQ.1, BA.5.3.1.1.1.1.1) [87][94][86][89]

Beta變異株 (Beta, B.1.351谱系) [A]

CAL.20C書面挪威語California-koronavarianten (Epsilon, B.1.427書面挪威語Lineage B.1.427B.1.429書面挪威語Lineage B.1.429) [B]

B.1.525英语SARS-CoV-2 Eta variant (Eta)

B.1.526英语SARS-CoV-2 Iota variant (Iota)

B.1.617谱系[39][106][107]

B.1.617.1英语SARS-CoV-2 Kappa variant (Kappa)

Delta變異株 (B.1.617.2) [96][A]

B.1.617.2.1德语B.1.617#B.1.617.2.1 (Delta Plus, AY.1) [97]

B.1.617.2.4.2 (Delta Plus, AY.4.2) [73][98]

B.1.617.3

B.1.618書面挪威語Lineage B.1.618 [99][100]

Mu變異株(B.1.621譜系)[101][102][103][104]

B.1.640 [105][87]

  1. ^ 1.0 1.1 1.2 1.3 1.4 1.5 高關注變異株英语Variant of concern
  2. ^ 美国疾病控制与预防中心宣布的引发关切的变种英语Variant of concern

關注度之基準

  1. 需要关注的变异株英语Variant of concern(英語:variant of concern,VOC[108]
  2. 需要留意的变异株英语Variant of interest(英語:variant of interest,VOI[108]
  3. 监视下的变异株英语Variant under monitoring(英語:variant under monitoring,VUM[108]

現階段的主流變異株

需要關注的變異株(VOC)

病毒变异是一个自然随机过程,並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。目前在世界的主要變異株为最早发现于非洲南部由希腊字母「Omicron」标记。

Omicron(B.1.1.529谱系)

B.1.1.529變異株(WHO命名為Omicron[109][110][111])是目前變異最多的嚴重特殊傳染性肺炎病毒。據媒體簡報會上發佈:這個變異株有超過50個突變[112],而單單在刺突蛋白的突變也有32種[110][113][112]

  • 於2021年11月,在非洲南部的波札那南非發現[112][114][111]
  • 2021年11月24日,升級為「VUM」等級。
  • 2021年11月26日,再升級為「VOC」等級。
  • 目前變種分支亞型:BA.1(標準亞型)、BA.2、BA.3、BA.4、BA.5,總共超過千種以上的「次分支」、「子代」及「重組」變異株。
目前「VOC-VOI」等級(需要留意)變異株
  • BA.2.86:被稱為「皮羅拉」(Pirola)
  • JN.1
目前「VOC-VUM」等級(監視)變異株
  • KP.2
  • KP.3
  • KP.3.1.1
  • JN.1.7
  • JN.1.18
  • LB.1
  • XEC

過去的主流變異株

需要关注的变异株(Previous VOC)

Alpha(B.1.1.7谱系)

B.1.1.7谱系,WHO命名为“Alpha”,又称VOC 202012/01,並称501Y.V1变种。部分與「N501Y」突變有關。有23個病毒基因變異點。

  • 在2020年9月,首次从英国東南方的肯特郡(Kent)所發現采集的样本中发现[115]
  • 2020年12月18日,升級為「VOC」等級。
  • 2022年3月9日,降級為「Previous VOC」等級。

Beta(B.1.351谱系)

B.1.351谱系,WHO命名為「Beta」,又称501Y.V2变种。與「N501Y」、「K417N」、「E484K」突變有關,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单克隆抗体的中和作用。当前尚未有证据表明该变种影響嚴重特殊傳染性肺炎的嚴重程度[117]。。

Gamma(P.1谱系)

P.1谱系,WHO命名為「Gamma」,又称501Y.V3变种。包括三個相關突變:「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,升級為「VOC」等級。
  • 2022年3月9日,降級為「Previous VOC」等級。

Delta(B.1.617.2谱系)

B.1.617谱系是2020年10月于印度发现的一种双突变變異株。直到2021年1月前,该變異株的感染人数都寥寥无几。4月时该變異株已经蔓延至超过20个国家,遍及南极洲和南美洲以外的所有大洲。[120][121][122]

在该變異株约15个谱系定义突变中包括刺突蛋白突变D111D(同义突变英语synonymous substitution)、G142D[123]、P681R、E484Q[107]、L452R[124],其中后两个突变可能会影响恢复期血浆单克隆抗体的中和作用。[125]

英国公共卫生部英语Public Health England于5月7日将B.1.617.2列为“高關注變異株英语Variant of concern”,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(Delta)变种。[128] 稍后WHO將B.1.617.2命名為「Delta」。

5月21日,越南宣布发现一种传播性更高,由Delta變異株加上Alpha變異株上突变的病毒株。[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Delta变种。[130]

据报道,Delta變異株基本传染数R0大约为6(有说法称其高达8或9)[131],是嚴重急性呼吸道症候群冠狀病毒2型原始毒株基本传染数的2倍以上。[132]

  • 2021年4月4日,為升級為「VOI」等級。
  • 2021年5月11日,為升級為「VOC」等級。
  • 2022年6月7日,降級為「Previous VOC」等級。

需要留意的变异株(Previous VOI)

Epsilon(B.1.427譜系、B.1.429譜系)

B.1.427譜系、B.1.429譜系,WHO命名為「Epsilon」,於2020年3月在美國加州首次發現。

  • 2021年3月5日,升級為「VOI」等級。
  • 2021年7月6日,降級為「Previous VOI」等級。

Zeta(P.2譜系)

P.2譜系,WHO命名為「Zeta」,於2020年4月在巴西里約熱內盧首次發現。

  • 2021年3月17日,升級為「VOI」等級。
  • 2021年7月6日,降級為「Previous VOI」等級。

Eta(B.1.525譜系)

B.1.525譜系,WHO命名為「Eta」,於2020年12月在奈及利亞首次發現。

  • 2021年3月17日,升級為「VOI」等級。
  • 2021年9月20日,降級為「Previous VOI」等級。

Iota(B.1.526譜系)

B.1.526譜系,WHO命名為「Iota」,於2020年11月在美國紐約首次發現。

  • 2021年3月20日,升級為「VOI」等級。
  • 2021年9月20日,降級為「Previous VOI」等級。

Theta(P.3譜系)

P.3譜系,WHO命名為「Theta」,於2021年1月在菲律賓首次發現。

  • 2021年3月24日,升級為「VOI」等級。
  • 2021年7月6日,降級為「Previous VOI」等級。

Kappa(B.1.617.1)

B.1.617譜系的三個子譜系之一當中的「B.1.617.1」,WHO命名為「Kappa」,於2020年10月在印度首次發現。

  • 2021年4月4日,升級為「VOI」等級。
  • 2021年9月20日,降級為「Previous VOI」等級。

Lambda(C.37谱系)

C.37譜系,WHO命名為「Lambda」,於2020年8月在秘魯首次發現。

  • 2021年6月14日,升級為「VOI」等級。
  • 2022年3月9日,降級為「Previous VOI」等級。

Mu(B.1.621譜系)

B.1.621譜系,WHO命名為「Mu」,於2021年1月在哥倫比亞首次發現。

  • 2021年8月30日,升級為「VOI」等級。
  • 2022年3月9日,降級為「Previous VOI」等級。

备注

  1. ^ 臺灣疾管署按美國CDC定義分三類,稱為:需留意變異株(Variants of Interest, VOI)、高關注變異株(Variants of Concern, VOC)、高衝擊變異株(Variant of High Consequence)。

参见

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