SARS-CoV-2 Theta variant

The Theta variant (P.3) was a SARS-CoV-2 variant of interest.^[1] It was first identified in the Philippines on February 18, 2021,^[2] and shortly thereafter detected in Japan on March 12, 2021.^[3]

The variant is distinct from those first discovered in the United Kingdom, South Africa, and Brazil, and is thought to pose a similar threat. It is more resistant to neutralizing antibodies, including those gained through vaccination, like how the South African and Brazilian variants appear to be.^[4]

Under the standardized nomenclature system established by the World Health Organization (WHO), lineage P.3 has been labeled Theta and was classified as a variant of interest rather than a variant of concern. As of July 2021, Theta is no longer considered a variant of interest by the WHO.^[1]

Classification

The Theta variant corresponds to PANGO lineage P.3 (B.1.1.28.3), which stems from B.1.1.28, the same parental lineage as P.1 (Gamma) and P.2 (Zeta).^[5] It also belongs to Nextstrain clade 21E and GISAID clade GR/1092K.V1.^[1] On March 17, 2021, it was designated as a variant under investigation (VUI) labeled VUI-21MAR-02 by Public Health England (PHE).^[6] On March 24, 2021, the World Health Organization (WHO) classified it as a variant of interest (VOI) and assigned it the Greek-letter name Theta. Then, on July 6, 2021, it was reclassified as a variant under monitoring (VUM), and again on August 17, 2021, as a previously circulating VOI because it no longer poses a major additional risk to global public health.^[1]

Mutations

Amino acid mutations of SARS-CoV-2 Theta variant plotted on a genome map of SARS-CoV-2 with a focus on the spike.^[7]

A total of 14 amino acid replacements were observed in all samples (labeled in red below), including seven spike protein mutations. Among the spike protein mutations, four have been previously associated with lineages of concern (i.e., E484K, N501Y, D614G, and P681H), while three additional replacements were observed towards the C-terminal region of the protein (i.e., E1092K, H1101Y, and V1176F). A single amino acid replacement at the N-terminus of ORF8 (i.e., K2Q) was also found in all samples. Three other mutations were seen in 32 of the 33 samples (labeled in green), including a three-amino acid deletion at the spike protein positions 141 to 143. Lastly, five synonymous mutations (labeled in gray) were also detected in all of the cases.^[8]

Mutation profile of Theta variant
Gene	Amino acid
ORF1ab	F924F
	D1554G
	S2433S
	L3201P
	D3681E
	N3928N
	L3930F
	P4715L
	A5692V
S	LGV141_143del
	E484K
	N501Y
	G593G
	D614G
	P681H
	S875S
	E1092K
	H1101Y
	V1176F
ORF8	K2Q
N	R203K
N	G204R

Characteristic mutations of Theta variant^[9]
Gene	Amino acid
ORF1a	D1554G
	S2625F
	D2980N
	L3201P
	D3681E
	L3930F
ORF1b	P314L
	L1203F
	A1291V
S	LGV141_143del
	E484K
	N501Y
	G593G
	D614G
	P681H
	S875S
	E1092K
	H1101Y
	V1176F
ORF8	K2Q
N	R203K
N	G204R

History

On February 18, 2021, the Department of Health (Philippines) confirmed the detection of two mutations of COVID-19 in Central Visayas after samples from patients were sent to undergo genome sequencing. The mutations, later named as E484K and N501Y, were detected in 37 out of 50 samples, with both mutations co-occurrent in 29 of these cases. There were no official names for the variants at the time, and the full sequence had yet to be identified.^[2] Japan then detected the variant when a traveler from the Philippines arrived at Narita International Airport in Tokyo on March 12, 2021.^[3] The following day, March 13, 2021, the Department of Health of the Philippines confirmed that these mutations constituted a new variant, which was designated as lineage P.3. On the same day, it also confirmed the country's first case of lineage P.1. Although lineages P.1 and P.3 stem from the same B.1.1.28 lineage, the department said that the impact of lineage P.3 on vaccine efficacy and transmissibility is yet to be ascertained.^[10]

On March 17, 2021, the United Kingdom confirmed its first two cases,^[11] while on April 30, 2021, Malaysia detected 8 cases of lineage P.3 in Sarawak.^[12]

Statistics

Confirmed cases by country (as of January 24, 2022)
Country	PANGOLIN^[13]	outbreak.info^[9]	Regeneron^[14]	Other sources
Philippines	455	513	516	461^[15]
USA	17	20	17
Germany	11	11	11
Malaysia	10	10	10	13^[16]
United Kingdom	9	9	9	10^[17]
Japan	7	8	8
Netherlands	7	7	7	4^[18]
Canada	5	5	5
Australia	3	3	4
Belgium	3	3	3
China^[a]	3	14	14
Guam	3	–	3
New Zealand	3	3	3
Norway	3	3	3
Singapore	3	3	3
Angola	2	2	2
South Korea	2	2	2
Sweden	2	2	2
Brazil	1	1	1
Finland	1	1	1
Total	550	620	624	488