2021, indicated that the gamma variant is 1.4–2.2 times more transmissible and was shown to be capable of evading 25–61% of inherited immunity from previous coronavirus diseases, leading to the possibility of reinfection after recovery from an earlier covid-19 infection. as for the fatality ratio, infections by gamma were also found to be 10–80% more lethal. a study found that people fully vaccinated with pfizer or moderna have significantly decreased neutralisation effect against gamma, although the actual impact on the course of the disease is uncertain. a pre-print study by the oswaldo cruz foundation published in early april found that the real-world performance of people with the initial dose of the sinovac's coronavac vaccine had approximately 50% efficacy rate. they expected the efficacy to be higher after the 2nd dose. as of july 2021, the study is ongoing. preliminary data from two studies indicate that the oxford–astrazeneca vaccine is effective against the gamma variant, although the exact level of efficacy has not yet been released. preliminary data from a study conducted by instituto butantan suggest that coronavac is effective against the gamma variant as well, and as of july 2021 has yet to be expanded to obtain definitive data. on 16 march 2022, the who has de-escalated the gamma variant and its subvariants to "previously circulating variants of concern". delta (lineage b.1.617.2) main article: sars-cov-2 delta variant the delta variant, also known as b.1.617.2, g/452r.v3, 21a or 21a/s:478k, was a globally dominant variant that spread to at least 185 countries. it was first discovered in india. descendant of lineage b.1.617, which also includes the kappa variant under investigation, it was first discovered in october 2020 and has since spread internationally. on 6 may 2021, british scientists declared b.1.617.2 (which notably lacks mutation at e484q) as a "variant of concern", labelling it voc-21apr-02, after they flagged evidence that it spreads more quickly than the original version of the virus and could spread quicker or as quickly as alpha. it carries l452r and p681r mutations in spike; unlike kappa it carries t478k but not e484q. on 3 june 2021, public health england reported that twelve of the 42 deaths from the delta variant in england were among the fully vaccinated, and that it was spreading almost twice as fast as the alpha variant. also on 11 june, foothills medical centre in calgary, canada reported that half of their 22 cases of the delta variant occurred among the fully vaccinated. in june 2021, reports began to appear of a variant of delta with the k417n mutation. the mutation, also present in the beta and gamma variants, raised concerns about the possibility of reduced effectiveness of vaccines and antibody treatments and increased risk of reinfection. the variant, called "delta with k417n" by public health england, includes two clades corresponding to the pango lineages ay.1 and ay.2. it has been nicknamed "delta plus" from "delta plus k417n". the name of the mutation, k417n, refers to an exchange whereby lysine (k) is replaced by asparagine (n) at position 417. on 22 june, india's ministry of health and family welfare declared the "delta plus" variant of covid-19 a variant of concern, after 22 cases of the variant were reported in india. after the announcement, leading virologists said there was insufficient data to support labelling the variant as a distinct variant of concern, pointing to the small number of patients studied. in the uk in july 2021, ay.4.2 was identified. alongside those previously mentioned it also gained the nickname 'delta plus', on the strength of its extra mutations, y145h and a222v. these are not unique to it, but distinguish it from the original delta variant. on 7 june 2022, the who has de-escalated the delta variant and its subvariants to "previously circulating variants of concern". previously circulating variants of interest (voi) pango lineage gisaid cladenextstrain cladeearliest samplesdate of voidate of designation country of samplingnotes p.2gr/484k.v220b/s.484k2020-042021-07-062021-08-17 zeta variant p.3gr/1092k.v121e2021-012021-07-062021-08-17 theta variant b.1.427b.1.429gh/452r.v121c2020-032021-07-062021-11-09 epsilon variant b.1.617.1 g/452r.v3 21b 2020-10 2021-09-20 kappa variant b.1.526 gh/253g.v1 21f 2020-11 2021-09-20 iota variant b.1.525 g/484k.v3 21d 2020-12 2021-09-20 eta variant c.37 gr/452q.v1 21g 2020-12 2021-06-14 2022-03-09 lambda variant b.1.621 gh 21h 2021-01 2021-08-30 2022-03-09 mu variant epsilon (lineages b.1.429, b.1.427, cal.20c) main article: sars-cov-2 epsilon variant the epsilon variant or lineage b.1.429, also known as cal.20c or ca vui1, 21c or 20c/s:452r, is defined by five distinct mutations (i4205v and d1183y in the orf1ab gene, and s13i, w152c, l452r in the spike protein's s-gene), of which the l452r (previously also detected in other unrelated lineages) was of particular concern. from 17 march to 29 june 2021, the cdc listed b.1.429 and the related b.1.427 as "variants of concern". as of july 2021, epsilon is no longer considered a variant of interest by the who, as it was overtaken by alpha. from september 2020 to january 2021, it was 19% to 24% more transmissible than earlier variants in california. neutralisation against it by antibodies from natural infections and vaccinations was moderately reduced, but it remained detectable in most diagnostic tests. epsilon (cal.20c) was first observed in july 2020 by researchers at the cedars-sinai medical center, california, in one of 1,230 virus samples collected in los angeles county since the start of the covid-19 epidemic. it was not detected again until september when it reappeared among samples in california, but numbers remained very low until november. in november 2020, the epsilon variant accounted for 36 per cent of samples collected at cedars-sinai medical center, and by january 2021, the epsilon variant accounted for 50 per cent of samples. in a joint press release by university of california, san francisco, california department of public health, and santa clara county public health department, the variant was also detected in multiple counties in northern california. from november to december 2020, the frequency of the variant in sequenced cases from northern california rose from 3% to 25%. in a preprint, cal.20c is described as belonging to clade 20c and contributing approximately 36% of samples, while an emerging variant from the 20g clade accounts for some 24% of the samples in a study focused on southern california. note, however, that in the us as a whole, the 20g clade predominates, as of january 2021. following the increasing numbers of epsilon in california, the variant has been detected at varying frequencies in most us states. small numbers have been detected in other countries in north america, and in europe, asia and australia. after an initial increase, its frequency rapidly dropped from february 2021 as it was being outcompeted by the more transmissible alpha. in april, epsilon remained relatively frequent in parts of northern california, but it had virtually disappeared from the south of the state and had never been able to establish a foothold elsewhere; only 3.2% of all cases in the united states were epsilon, whereas more than two-thirds were alpha. zeta (lineage p.2) main article: sars-cov-2 zeta variant zeta variant or lineage p.2, a sub-lineage of b.1.1.28 like gamma (p.1), was first detected in circulation in the state of rio de janeiro; it harbours the e484k mutation, but not the n501y and k417t mutations. it evolved independently in rio de janeiro without being directly related to the gamma variant from manaus. though previously zeta was labeled a variant of interest, as of july 2021, it is no longer considered as such by the who. eta (lineage b.1.525) main article: sars-cov-2 eta variant the eta variant or lineage b.1.525, also called vui-21feb-03 (previously vui-202102/03) by public health england (phe) and formerly known as uk1188, 21d or 20a/s:484k, does not carry the same n501y mutation found in alpha, beta and gamma, but carries the same e484k-mutation as found in the gamma, zeta, and beta variants, and also carries the same δh69/δv70 deletion (a deletion of the amino acids histidine and valine in positions 69 and 70) as found in alpha, n439k variant (b.1.141 and b.1.258) and y453f variant (cluster 5). eta differs from all other variants by having both the e484k-mutation and a new f888l mutation (a substitution of phenylalanine (f) with leucine (l) in the s2 domain of the spike protein). as of 5 march 2021, it had been detected in 23 countries. it has also been reported in mayotte, the overseas department/region of france. the first cases were detected in december 2020 in the uk and nigeria, and as of 15 february 2021, it had occurred in the highest frequency among samples in the latter country. as of 24 february 56 cases were found in the uk. denmark, which sequences all its covid-19 cases, found 113 cases of this variant from 14 january to 21 february 2021, of which seven were directly related to foreign travel to nigeria. as of july 2021, uk experts are studying it to ascertain how much of a risk it could be. it is currently regarded as a "variant under investigation", but pending further study, it may become a "variant of concern". ravi gupta, from the university of cambridge said in a bbc interview that lineage b.1.525 appeared to have "significant mutations" already seen in some of the other newer variants, which means their likely effect is to some extent more predictable. theta (lineage p.3) on 18 february 2021, the department of health of the 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 were later named as e484k and n501y, which were detected in 37 out of 50 samples, with both mutations co-occurrent in 29 out of these. on 13 march, the department of health confirmed the mutations constitutes a variant which was designated as lineage p.3. on the same day, it also confirmed the first covid-19 case caused by the gamma variant in the country. the philippines had 98 cases of the theta variant on 13 march. on 12 march it was announced that theta had also been detected in japan. on 17 march, the united kingdom confirmed its first two cases, where phe termed it vui-21mar-02. on 30 april 2021, malaysia detected 8 cases of the theta variant in sarawak. as of july 2021, theta is no longer considered a variant of interest by the who. iota (lineage b.1.526) main article: sars-cov-2 iota variant in november 2020, a mutant variant was discovered in new york city, which was named lineage b.1.526. as of 11 april 2021, the variant has been detected in at least 48 u.s. states and 18 countries. in a pattern mirroring epsilon, iota was initially able to reach relatively high levels in some states, but by may 2021 it was outcompeted by the more transmissible delta and alpha. kappa (lineage b.1.617.1) main article: sars-cov-2 kappa variant the kappa variant is one of the three sublineages of lineage b.1.617. it is also known as lineage b.1.617.1, 21b or 21a/s:154k, and was first detected in india in december 2020. by the end of march 2021, kappa accounted for more than half of the sequences being submitted from india. on 1 april 2021, it was designated a variant under investigation (vui-21apr-01) by public health england. it has the notable mutations l452r, e484q, p681r. lambda (lineage c.37) main article: sars-cov-2 lambda variant the lambda variant, also known as lineage c.37, was first detected in peru in august 2020 and was designated by the who as a variant of interest on 14 june 2021. it spread to at least 30 countries around the world and, as of july 2021, it is unknown whether it is more infectious and resistant to vaccines than other strains. on 16 march 2022, the who has de-escalated the lambda variant to "previously circulating variants of concern". mu (lineage b.1.621) main article: sars-cov-2 mu variant the mu variant, also known as lineage b.1.621, was first detected in colombia in january 2021 and was designated by the who as a variant of interest on 30 august 2021. there have been outbreaks in south america and europe. on 16 march 2022, the who has de-escalated the mu variant and its subvariants to "previously circulating variants of concern". formerly monitored variants (who) the variants listed below were once listed under variants under monitoring, but were reclassified due to either no longer circulating at a significant level, not having had a significant impact on the situation, or