KP.3.3 + ORF1a:I1367L (369 seq, 5 continents, 25 countries; Jul 31)

[ryhisner]

Description
Sub-lineage of: KP.3.3
Earliest sequence: 2024-5-13, Luxembourg — EPI_ISL_19229409
Most recent sequence: 2024-7-22, Denmark — EPI_ISL_19299736
Continents circulating: Europe (328), North America (32), Africa (1), Asia (1), Oceania (1)
Countries circulating: Germany (130), Netherlands (51), France (30), Denmark (27), England (27), Spain (17), Scotland (9), USA (8), Luxembourg (7), Wales (7), Austria (5), Iceland (3), Ireland (3), Italy (3), Norway (3), Belgium (2), Canada (2), Canary Islands (2), Croatia (2), Switzerland (2), Australia (1), Kenya (1), Northern Ireland (1), Slovenia (1), Taiwan (1)
Number of Sequences: 355
GISAID Nucleotide Query: A4364C, T8263C, -A3081C
CovSpectrum Query: [2-of: A4364C, T8263C] & !A3081C
Substitutions on top of KP.3.3:
ORF1a: I1367L (NSP3_I549L)

Nucleotide: A4364C, T8263C

USHER Tree
https://nextstrain.org/fetch/raw.githubusercontent.com/ryhisner/jsons2/main/KP.3.3_I1367L.json

Note that the poor quality of a large number of these genomes, particular those from Germany and Luxembourg, makes the Usher tree appear as if there is far more diversity than there actually is. If artifactual reversions could be removed, this would be a much more compact tree.

Evidence
ORF1a:I1367L (NSP3_I549L) has been a very rare mutation. Excluding BA.2.86* (which are virtually all in this lineage), CovSpectrum counts only 220 sequences ever. Restricting the search to "good" sequences returns just 116 sequences. But ORF1a:I1367L has been a prominent mutation in many chronic-infection sequences.

I keep a large list of such sequences, and after adjusting for mutation frequency in circulating lineages, ORF1a:I1367L is the 19th most frequent chronic-infection mutation (considering only mutations that appear at least 10 times independently). Restricting to sequences that appear at least 20 times independently, it comes in at #8.

But as described above, it's a mutation that has been virtually nonexistent in circulating lineages, which is why it's remarkable that it has succeeded so well in KP.3.3 over the last two months, primarily in Europe, but also with detections in five of the six other inhabited continents.

Note: A large number of these genomes are really, really low-quality sequences from Germany, a country heretofore known for its craftsmanship and high-quality productions. The spike protein in most of these sequences is almost nonexistent downstream of S:210, but ORF1a is reasonably well covered.

Genomes

Genomes

EPI_ISL_19189948,EPI_ISL_19189954,EPI_ISL_19189956,EPI_ISL_19192347,EPI_ISL_19192359,EPI_ISL_19197977,EPI_ISL_19198271,EPI_ISL_19203525,EPI_ISL_19205892,EPI_ISL_19206086,EPI_ISL_19206089,EPI_ISL_19209798,EPI_ISL_19210151,EPI_ISL_19210272,EPI_ISL_19210350,EPI_ISL_19220531,EPI_ISL_19220631,EPI_ISL_19221125,EPI_ISL_19221141,EPI_ISL_19221582,EPI_ISL_19221672,EPI_ISL_19221719,EPI_ISL_19225081,EPI_ISL_19225216,EPI_ISL_19225233,EPI_ISL_19225522,EPI_ISL_19226128,EPI_ISL_19229053,EPI_ISL_19229320,EPI_ISL_19229323,EPI_ISL_19229328,EPI_ISL_19229331,EPI_ISL_19229338-19229340,EPI_ISL_19229366,EPI_ISL_19229401,EPI_ISL_19229409,EPI_ISL_19229494,EPI_ISL_19229516,EPI_ISL_19229541,EPI_ISL_19229586,EPI_ISL_19229810,EPI_ISL_19229858,EPI_ISL_19230365,EPI_ISL_19232258,EPI_ISL_19232262,EPI_ISL_19232336,EPI_ISL_19232442,EPI_ISL_19232603,EPI_ISL_19232952,EPI_ISL_19232965,EPI_ISL_19232975,EPI_ISL_19233071,EPI_ISL_19239301,EPI_ISL_19239305,EPI_ISL_19239914,EPI_ISL_19239964,EPI_ISL_19240153,EPI_ISL_19240384,EPI_ISL_19240386,EPI_ISL_19240803,EPI_ISL_19240811,EPI_ISL_19240871,EPI_ISL_19243713,EPI_ISL_19243799,EPI_ISL_19243913,EPI_ISL_19244005,EPI_ISL_19244014,EPI_ISL_19244164,EPI_ISL_19244215-19244216,EPI_ISL_19244231-19244232,EPI_ISL_19244236,EPI_ISL_19244250,EPI_ISL_19244324,EPI_ISL_19244358,EPI_ISL_19244493,EPI_ISL_19244510,EPI_ISL_19244586,EPI_ISL_19244589,EPI_ISL_19244592,EPI_ISL_19244603,EPI_ISL_19244610,EPI_ISL_19244620-19244621,EPI_ISL_19244623,EPI_ISL_19244626-19244627,EPI_ISL_19244629,EPI_ISL_19244639,EPI_ISL_19244646,EPI_ISL_19244651,EPI_ISL_19244660,EPI_ISL_19244669,EPI_ISL_19244677,EPI_ISL_19244680,EPI_ISL_19244685-19244686,EPI_ISL_19244692,EPI_ISL_19244695,EPI_ISL_19244707-19244708,EPI_ISL_19244713-19244715,EPI_ISL_19244717-19244718,EPI_ISL_19244725,EPI_ISL_19244729,EPI_ISL_19244732,EPI_ISL_19244739,EPI_ISL_19244746,EPI_ISL_19244754,EPI_ISL_19244758,EPI_ISL_19244762-19244763,EPI_ISL_19244771-19244772,EPI_ISL_19250949,EPI_ISL_19251980,EPI_ISL_19252426,EPI_ISL_19252437,EPI_ISL_19252882,EPI_ISL_19252918,EPI_ISL_19253375,EPI_ISL_19254246,EPI_ISL_19254266,EPI_ISL_19254268,EPI_ISL_19254294,EPI_ISL_19254497,EPI_ISL_19254630,EPI_ISL_19256831,EPI_ISL_19256927,EPI_ISL_19257044,EPI_ISL_19258203,EPI_ISL_19258206,EPI_ISL_19258208,EPI_ISL_19258214-19258215,EPI_ISL_19258414,EPI_ISL_19260250,EPI_ISL_19261237,EPI_ISL_19261271,EPI_ISL_19261308,EPI_ISL_19261377,EPI_ISL_19261460,EPI_ISL_19261546,EPI_ISL_19261560,EPI_ISL_19261576,EPI_ISL_19261732-19261735,EPI_ISL_19261854,EPI_ISL_19261885,EPI_ISL_19261908,EPI_ISL_19261942,EPI_ISL_19261953,EPI_ISL_19261955,EPI_ISL_19261989,EPI_ISL_19262035,EPI_ISL_19262045,EPI_ISL_19262062,EPI_ISL_19262101,EPI_ISL_19262108,EPI_ISL_19262112,EPI_ISL_19264938,EPI_ISL_19264941,EPI_ISL_19265031,EPI_ISL_19265173-19265174,EPI_ISL_19265215,EPI_ISL_19267201,EPI_ISL_19267536-19267537,EPI_ISL_19267565,EPI_ISL_19267938-19267939,EPI_ISL_19268291,EPI_ISL_19268296,EPI_ISL_19269868,EPI_ISL_19270124,EPI_ISL_19270168,EPI_ISL_19270189,EPI_ISL_19270222,EPI_ISL_19270860,EPI_ISL_19270877,EPI_ISL_19272196,EPI_ISL_19272658,EPI_ISL_19273409,EPI_ISL_19273448,EPI_ISL_19273564,EPI_ISL_19273801,EPI_ISL_19276082,EPI_ISL_19276391,EPI_ISL_19276538,EPI_ISL_19277115,EPI_ISL_19279089,EPI_ISL_19279684,EPI_ISL_19279686,EPI_ISL_19279787,EPI_ISL_19280039-19280040,EPI_ISL_19280440,EPI_ISL_19281116,EPI_ISL_19281361,EPI_ISL_19281374,EPI_ISL_19281386,EPI_ISL_19281411,EPI_ISL_19281844,EPI_ISL_19283606,EPI_ISL_19283735,EPI_ISL_19283737,EPI_ISL_19283743,EPI_ISL_19283747,EPI_ISL_19283753-19283754,EPI_ISL_19283761,EPI_ISL_19283763-19283764,EPI_ISL_19283771,EPI_ISL_19283776,EPI_ISL_19283779-19283781,EPI_ISL_19283787,EPI_ISL_19283790,EPI_ISL_19283795,EPI_ISL_19283802,EPI_ISL_19283806,EPI_ISL_19283809-19283810,EPI_ISL_19283815-19283816,EPI_ISL_19283818,EPI_ISL_19283820,EPI_ISL_19283825,EPI_ISL_19283836,EPI_ISL_19283840-19283841,EPI_ISL_19283844,EPI_ISL_19283850,EPI_ISL_19283852-19283853,EPI_ISL_19283857,EPI_ISL_19283862,EPI_ISL_19283867,EPI_ISL_19283876,EPI_ISL_19283886,EPI_ISL_19283893,EPI_ISL_19283903,EPI_ISL_19283907,EPI_ISL_19283910,EPI_ISL_19283915-19283916,EPI_ISL_19283918,EPI_ISL_19283920,EPI_ISL_19283929-19283930,EPI_ISL_19283933,EPI_ISL_19283938,EPI_ISL_19283948,EPI_ISL_19283951-19283952,EPI_ISL_19283961,EPI_ISL_19283967,EPI_ISL_19283970,EPI_ISL_19283976,EPI_ISL_19285261,EPI_ISL_19285640,EPI_ISL_19285647,EPI_ISL_19285703,EPI_ISL_19285719,EPI_ISL_19285736,EPI_ISL_19285761,EPI_ISL_19285791,EPI_ISL_19285829,EPI_ISL_19285900,EPI_ISL_19285923,EPI_ISL_19285925,EPI_ISL_19287461,EPI_ISL_19287888,EPI_ISL_19288018,EPI_ISL_19288067,EPI_ISL_19288090,EPI_ISL_19288094,EPI_ISL_19288105,EPI_ISL_19288145,EPI_ISL_19288275,EPI_ISL_19288355,EPI_ISL_19288358,EPI_ISL_19288361,EPI_ISL_19288365,EPI_ISL_19288367,EPI_ISL_19288373,EPI_ISL_19288375,EPI_ISL_19288397,EPI_ISL_19289755,EPI_ISL_19289882,EPI_ISL_19289951,EPI_ISL_19291357,EPI_ISL_19291378-19291379,EPI_ISL_19291453,EPI_ISL_19291476,EPI_ISL_19291853,EPI_ISL_19291866,EPI_ISL_19292078,EPI_ISL_19292226,EPI_ISL_19292333,EPI_ISL_19292471,EPI_ISL_19292781,EPI_ISL_19292796,EPI_ISL_19292800,EPI_ISL_19292805,EPI_ISL_19292813-19292814,EPI_ISL_19292828,EPI_ISL_19292833,EPI_ISL_19292835,EPI_ISL_19292860,EPI_ISL_19292878,EPI_ISL_19292898,EPI_ISL_19292949,EPI_ISL_19293173,EPI_ISL_19293222,EPI_ISL_19293230,EPI_ISL_19293263,EPI_ISL_19293272,EPI_ISL_19293305,EPI_ISL_19293346,EPI_ISL_19293371,EPI_ISL_19293373,EPI_ISL_19294999,EPI_ISL_19295180,EPI_ISL_19295187,EPI_ISL_19296640,EPI_ISL_19296980,EPI_ISL_19297047,EPI_ISL_19297062,EPI_ISL_19297927-19297928,EPI_ISL_19298060,EPI_ISL_19298340,EPI_ISL_19299642,EPI_ISL_19299655,EPI_ISL_19299684,EPI_ISL_19299688,EPI_ISL_19299722,EPI_ISL_19299724,EPI_ISL_19299728,EPI_ISL_19299736,EPI_ISL_19299816,EPI_ISL_19299821,EPI_ISL_19299839,EPI_ISL_19299895,EPI_ISL_19299961,EPI_ISL_19300044,EPI_ISL_19300160,EPI_ISL_19300321,

[ryhisner]

@FedeGueli has kindly pointed out to me that there is an S:S31del branch in this lineage. Just five sequences at the moment, but all collected very recently, with collection dates June 28 and July 11, 15, 16, 17.

Countries are USA (one New York, one Florida), Spain (travel to USA), Canary Islands, and England.

Preliminary query for that branch would be: A4364C, T8263C, -A3081C, del21653_21655

Genomes

EPI_ISL_19258203, EPI_ISL_19289755, EPI_ISL_19296640, EPI_ISL_19298060, EPI_ISL_19298340

[FedeGueli]

@FedeGueli has kindly pointed out to me that there is an S:S31del branch in this lineage. Just five sequences at the moment, but all collected very recently, with collection dates June 28 and July 11, 15, 16, 17.

Countries are USA (one New York, one Florida), Spain (travel to USA), Canary Islands, and England.

Preliminary query for that branch would be: A4364C, T8263C, -A3081C, del21653_21655

Genomes

Thanks @ryhisner i have proposed in parallel the S:S31del sublineage that, with the query: G3971A,C25416T,T8263C,T3565C, is already 7 and growing ( i think that the count is different for the usual Danish undeletion at S:31!)
proposed here: cov-lineages/pango-designation#2704

[FedeGueli]

already 369

[FedeGueli]

Designated KP.3.3.4 via cov-lineages/pango-designation@5718a44