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SARS-CoV-2 Gamma variant

SARS-CoV-2 Gamma variant

Gamma variant, also known as lineage P.1,[a] is one of the variants of SARS-CoV-2, the virus that causes COVID-19.[6] This variant of SARS-CoV-2 has been named lineage P.1 and has 17 amino acid changes, ten of which are in its spike protein, including these three designated to be of particular concern: N501Y, E484K and K417T.[5][7] This variant of SARS-CoV-2 was first detected by the National Institute of Infectious Diseases (NIID), Japan, on 6 January 2021 in four people who had arrived in Tokyo having visited Amazonas, Brazil, four days earlier.[5][8] It was subsequently declared to be in circulation in Brazil.[5] Under the simplified naming scheme proposed by the World Health Organization, P.1 has been labeled Gamma variant, and is considered a variant of concern.[9]

Total number of P.1 sequences by country as of 21 April 2021[1]
Legend:
1,000+ confirmed sequences
500–999 confirmed sequences
100–499 confirmed sequences
2–99 confirmed sequences
1 confirmed sequence
None or no data available

P.1 caused widespread infection in early 2021 in the city of Manaus, the capital of Amazonas, although the city had already experienced widespread infection, in May 2020,[10] with a study,[11] indicating high seroprevalence of antibodies for SARS-CoV-2.[12] A research article published in Science Journal indicate that P.1 diseased people has greater chance of transmissibility and death than B.1.1.28 infected.

P.1 comprises the two distinct subvariants 28-AM-1 and 28-AM-2, which both carry the K417T, E484K, N501Y mutations, and both developed independently of each other within the same Brazilian Amazonas region.[13]

P.1 is notably different from the other Brazilian P.2 lineage. In particular, P.2 only carries the E484K mutation and has neither of the other two mutations of concern, N501Y and K417T.[13][7]

Contents

TaxonomyEdit

Initial reports claimed that both P.1 and P.2 were two separate and different descendants of the Brazilian B.1.1.248 variant.[14][15] However, B.1.1.248 later lost its status as a distinct variant and was reclassified to B.1.1.28.[16] P.1 has also been called B.1.1.28.1,[17] while P.2 has been B.1.1.28.2 or VUI-202101/01.[18] Since only three sublevels are permitted in the PANGO Lineage system of nomenclature, hence the designation of B.1.1.28.1 to P.1 and B.1.1.28.2 to P.2.[5][19]
ResearchEdit

On 12 January 2021, the Brazil–United Kingdom CADDE Centre confirmed 13 local cases of the P.1 lineage in Manaus, Amazonas state, the largest city of the Amazon rain forest.[5] The new lineage was absent in 27 samples collected from March to November from Manaus, but it was identified for the same city in 42% (n=13/31) of the samples collected 15–23 December 2020, followed by 52.2% (n=35/67) during 15–31 December and 85.4% (n=41/48) during 1–9 January 2021. Most notably, the P.2 was rapidly outcompeted by P1 going from the second half of December to 1–9 January, where the P.2 variant share for Manaus decreased from 25.4% to 6.3%.[5][20]

A study of 180 sequenced Brazilian samples collected in the state of Rio de Janeiro during 2020, identified emergence of the novel P.2 lineage of SARS-CoV-2 (originating from B.1.1.28). P.2 was first detected by genome sequencing in October 2020, but it was estimated to have emerged in early July 2020.[21] As of December 2020, although having significantly increased in frequency throughout the state, it was still largely confined to the state capital Rio de Janeiro. In May 2020 the main variants behind the COVID-19 positives were B.1.1.33 (70%) and B.1.1.28 (20%), whereas by September the main variants were B.1.1.33 (50%) and B.1.1.28 (40%), with no detected presence of P.2, while during October and November P.2 was the most common variant with a share close to 50% (according to the Pangolin tool).[22] The study also found the E484K mutation as "widely spread" across all analysed P.2 samples (36 out of 38).[22]

Researchers at the Oswaldo Cruz Foundation published a preprint genomic epidemiology study of 250 collected genomes from different places in Amazonas and found that P.1 infections can produce nearly 10 times more viral load than in other COVID-19-infected persons involving B.1.1.28 and B.1.195 lineages. The variant also showed 2.2 times higher transmissibility with the same ability to infect both adults (18–59 years old) and older persons (60 years old and higher), suggesting P.1 lineages are more successful at infecting younger humans with no gender differential.[23]

The Centre for Arbovirus Discovery, Diagnosis, Genomics and Epidemiology (CADDE) produced another journal article of samples collected in Manaus between November 2020 and January 2021. The study indicated P.1 lineage to be ≈2.0 times (50% CrI, 1.7–2.4 times) more transmissible and was shown to be capable of evading ≈32% (50% CrI, 21–46%) of inherited immunity from previous coronavirus diseases, leading to the possibility of reinfection. These increased statistics also had the same reflection in fatality, in that P.1 infections can be ≈50% (50% CrI, 20–90%) more lethal.[24][25][26] As part of ongoing research, the variant's capacity to neutralise antibodies has been evaluated by scientists in a published preprint work demonstrating that 8 CoronaVac-immunised persons had a poor blood plasma response against lineage P.1. Since the study only had a small number of participants, it was not possible to establish any statistical conclusion as a larger number of vaccinated people would need to be studied.[27] Scientists at MIT, Harvard and Cambridge, and hospitals physicians in Boston, corroborated that people fully vaccinated with Pfizer and Moderna vaccines have significantly decreased neutralisation with P.1—in a preprint work.[28]
MutationsEdit
Defining mutations in Lineage P.1GeneAmino acid
ORFlab synT733C
synC2749T
S1188L
K1795Q
del11288-11296 (3675-3677 SGF)
synC12778T
synC13860T
E5665D
Spike L18F
T20N
P26S
D138Y
R190S
K417T
E484K
N501Y
H 655Y
T1027I
ORF8 E92K
ins28269-28273
N P80R
Source: Faria et al. (2021), Figure 1.B

Variants of SARS-CoV-2 As well as having eight mutations (four of these synonymous genetic mutations) in its open reading frames (ORF1a and ORF1b) – one of which is a set of deletions – Lineage P.1 has 10 defining mutations in its spike protein, including N501Y and E484K. It also has two mutations – one an insertion – in its ORF8 region and one in its N region.[5][29]
Descendant and sublineagesEdit

Coronavirus variant B.1.1.28 has originated four known lineages classified as variant of interest (VOI) or variant of concern (VOC): lineages P.1, P.2, P.3 and P.4.

The P.2 lineage (B.1.1.28.2), first detected in October 2020 in the state of Rio de Janeiro, Brazil, only shares one mutation of concern with P.1, which is the E484K.[30] The other P.2 mutations are without concern and rarely found for other variants. The five P.2-specific mutations are: E484K in S-gene, A119S in N-gene, 5’UTR C100U, plus L3468V and synC11824U in ORF1ab-gene. Other mutations commonly found in P.2 are: 3’UTR C29754U, F120F (synC28253U) in ORF8, M234I in the N-gene, plus L3930F and synA12964G in ORF1ab.[21]

The P.3 variant was first identified in the Philippines on 18 February 2021 when two mutations of concern were detected in Central Visayas.[31]

The remaining B.1.1.28 derivative virus is the P.4 lineage. Although researchers have not identified its precise origin, it was first sequenced in Itirapina, Brazil, and was already circulating in various municipalities in the state of São Paulo of the same country. It carries a mutation of concern in the spike protein called L452R which is also present in B.1.617 detected in India, B.1.427 and B.1.429 from California, United States.[32][33] The branch of this lineage is P.4.1 (VUI-NP13L)—suspected to have arisen in Goiás, Brazil, around June–July 2020— also rapidly spread to the southeast of the country, where for example Taquara had its first genome sequence, and to the northeast of the nation. It was detected internationally, with reported cases in Japan, Netherlands and England. The P.4.1 has V1176F and D614G mutations in spike protein.[34]
DetectionEdit

Following its detection, genome data for four samples of the new variant were shared to GISAID having been assigned the ID range: EPI_ISL_792680 to EPI_ISL_792683.[35]
Circulation of Lineage P.1Edit
Development of Variant P.1
(share of analyzed SARS-CoV-2–positive tests in a given week)
CountryRegionSectorTestWeek 12[36]Week 13Week 14[37]Week 15Week 16Week 17

Peru Lima Lima Metropolitana 39.70%
Lima Este 63.20%
Lima Norte 50.00%
Lima Sur 41.90%
Central Lima 25.00%
Cajamarca Unknown 75.00%
Cuzco Unknown 70.00%
Madre de Dios Unknown 52.50%
Ucayali Unknown 47.60%
Piura Unknown 25.00%
La Libertad Unknown 25.00%
Ayacucho Unknown 20.00%
Loreto Unknown 08.10% 08.10%
Ancash Unknown 02.50%

StatisticsEdit
Cases by countryCountryConfirmed casesSuspected casesFirst detectionReferences