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Update on SARS-CoV-2 variants. WHO
WHO, in collaboration with national authorities, institutions and researchers, routinely assesses if variants of SARS-CoV-2 result in changes in transmissibility, clinical presentation and severity, or if they result in changes in public health and social measures (PHSM) implementation by national health authorities. Systems have been established to detect “signals” of potential variants of concern (VOCs) or variants of interest (VOIs) and assess these based on the risk posed to global public health (see also working definitions). National authorities may choose to designate other variants of local interest/concern. Detailed information on currently circulating VOCs and VOIs is available in previously published editions of the Weekly Epidemiological Update. Here we provide information on a newly designated VOC within lineage B.1.617, and provide an update on the geographical distribution, and emerging evidence surrounding phenotypic characteristics of all designated VOIs and VOCs.
Newly designated VOC within lineage B.1.617
In consultation with the WHO SARS-CoV-2 Virus Evolution Working Group, WHO has determined that viruses within the lineage B.1.617 have been characterized as a VOC. B.1.617 contains three sub-lineages (Table 2), which differ by few but potentially relevant mutations in the spike protein as well as prevalence of detection globally. As of 11 May, over 4500 sequences have been uploaded to GISAID and assigned to B.1.617 from 44 countries in all six WHO regions, and WHO has received reports of detections from five additional countries (Figure 3). Though there may be important differences among the three sublineages, currently available evidence is too limited for VOI/VOC characterization by sublineage. Future delineation of sublineages as VOIs/VOCs may be possible as our understanding by sublineage and relative importance of their epidemiology increases. At the present time, WHO has designated B.1.617 as a VOC based on early evidence of phenotypic impacts compared to other circulating virus variants, namely: • B.1.617 sublineages appear to have higher rates of transmission, including observed rapid increases in prevalence in multiple countries (moderate evidence available for B.1.617.1 and B.1.617.2), and • Preliminary evidence suggests potential reduced effectiveness of Bamlanivimab, a monoclonal antibody used for COVID-19 treatment, and potentially slightly reduced susceptibility to neutralisation antibodies (limited evidence available for B.1.617.1).
Viruses in the B.1.617 lineage were first reported in India in October 2020. The resurgence in COVID-19 cases and deaths in India has raised questions on the potential role of B.1.617 and other variants (e.g., B.1.1.7) in circulation. A recent risk assessment of the situation in India conducted by WHO found that resurgence and acceleration of COVID-19 transmission in India had several potential contributing factors, including increase in the proportion of cases of SARS-CoV-2 variants with potentially increased transmissibility; several religious and political mass gathering events which increased social mixing; and, under use of and reduced adherence to public health and social measures (PHSM). The exact contributions of these each of these factors on increased transmission in India are not well understood. Approximately 0.1% of positive samples in India have been sequenced and uploaded to GISAID to identify SARS-CoV-2 variants. The prevalence of several VOCs including B.1.1.7 and B.1.617 sublineages increased concurrent to the surge in COVID-19 cases reported in India. While B.1.1.7 and B.1.617.1 variants have begun to wane in recent weeks, a marked increase in the proportion of viruses sequenced as B.1.617.2 has been observed over the same period. Since the identification of these variants through late April 2021, B.1.617.1 and B.1.617.2 accounted for 21% and 7% of sequenced samples from India, respectively.a Preliminary analyses conducted by WHO using sequences submitted to GISAID suggests that B.1.617.1 and B.1.617.2 have a substantially higher growth rate than other circulating variants in India, suggesting potential increased transmissibility compared. Too few sequences of B.1.617.3 have been detected to date to assess its relative transmissibility. Other studies suggest that the case numbers increased more rapidly during the most recent surge when variants B.1.1.7 and B.1.617 were circulating, compared to the first surge (June to October 2020). b A structural analysis of B.1.617 receptor binding domain (RBD) mutations (L452R and E484Q, along with P681R in the furin cleavage site) suggest that mutations in these variants may result in increased ACE2 binding and rate of S1-S2 cleavage resulting in better transmissibility, and possibly capacity to escape binding and neutralization by some monoclonal antibodies.c In a preliminary study on hamsters, infection with B.1.617.1 resulted in increased body weight loss, higher viral load in lungs and pronounced lung lesions as compared to B.1 variants (D614G).
Potential impacts of B.1.617 lineage on effectiveness of vaccines or therapeutics, or reinfection risks, remain uncertain. Preliminary laboratory studies awaiting peer review suggest a limited reduction in neutralisation by antibodies; however, real-world impacts may be limited.e One study found a seven-fold reduction in neutralization effectiveness against B.1.617.1 of antibodies generated by vaccination with Moderna – mRNA1273 and Pfizer BioNTech-Comirnaty vaccines. f A second study also found a reduction in neutralization against virus carrying the E484Q mutation (contained in B.1.617.1 and B.1.617.3) for Pfizer BioNTech – Comirnaty vaccine, similar to that found with the E484K mutation.g A third study reviewing a limited sample of convalescent sera of COVID-19 cases (n=17) and sera from recipients of the Bharat – Covaxin vaccine (n=23) concluded that most neutralizing activity against B.1.617 was retained.e A fourth study reported an approximately three-fold decrease in neutralization activity by plasma from recipients of Pfizer BioNTech – Comirnaty vaccine (n=15) against B.1.617, and a limited two-fold decrease by convalescent sera from cases with severe COVID-19 (n=15). The same study showed that B.1.617.1 (with additional spike mutations R21T, and Q218H) mediates increased entry into certain human and intestinal cell lines, and was resistant to the monoclonal antibody Bamlanivimab; however, it was efficiently inhibited by Imdevimab and by a cocktail of Casirivimab and Imdevimab.e Outside of India, the United Kingdom has reported the largest number of cases sequenced as B.1.617 sublineages, and recently designated B.1.617.2 as a national variant of concern. This follows a recent steep increase in the number of cases sequenced as B.1.617 sublineages, and a national assessment that characterized B.1.617.2 as at least equivalent in terms of transmissibility as VOC B.1.1.7; however, they noted insufficient data to assess the potential for immune escape.h As of 5 May, the United Kingdom has reported 520 genomically confirmed B.1.617.2 cases (of which approximately two-thirds were domestically acquired), 261 confirmed B.1.617 cases (without further delineation), and nine confirmed B.1.617.3 cases.i Further robust studies into the phenotypic impacts of these variants, including impacts on epidemiological characteristics (transmissibility, severity, re-infection risk, etc.) and impact on countermeasures, are urgently needed.
Other VOCs
As surveillance activities to detect SARS-CoV-2 variants are strengthened at local and national levels, including by strategic genomic sequencing, the number of countries/areas/territories (hereafter countries) reporting VOCs and VOIs has continued to increase. Since our last update on 4 May, VOC 202012/01 has been detected in seven additional countries, variant 501Y.V2 in five additional countries, and variant P.1 in four additional countries. As of 11 May, a total 149 countries have reported VOC 202012/01 (Figure 4), 102 countries variant 501Y.V2 (Figure 5), and 60 countries variant P.1 (Figure 6) – see also Annex 2. The information presented here should be interpreted with due consideration of surveillance limitations, including differences in sequencing capacities and prioritization of samples for sequencing between countries.
Vaccine performance against VOCs
Available evidence on vaccine performance against VOCs has been highlighted in previous editions of the Weekly Epidemiological Update, most recently 27 April, and is summarised in Table 4.
Since the update on 27 April, two studies from Israel and another from Qatar offer further evidence that Pfizer BioNTech-Comirnaty vaccine provides similar protection against B.1.1.7 disease as that reported in clinical trials.47 Both studies from Israel (one published and one preprint) used national surveillance data and found high vaccine effectiveness after the second dose. The published study estimated a vaccine effectiveness of 98.1% (95% CI: 97.6-98.5), 98.0% (97.7-98.3), 97.7% (97.5-97.9), 96.5% (96.3-96.8), and 93.8% (93.3-94.2) against death, hospitalization, symptomatic disease, infection, and asymptomatic infection ≥ 14 days post second dose, respectively, in a setting where B.1.1.7 accounted for 95% of documented SARSCoV-2 cases.2 The preprint from Israel reported similar findings.1 In addition, the study from Qatar reports effectiveness of the vaccine to be 89.5% (95% CI: 85.9-92.3) against documented B.1.1.7 infection and 100% (95% CI: 81.7-100.0) against documented B.1.1.7 severe disease ≥ 14 days post second dose.3 The study also evaluated effectiveness of the Pfizer BioNTech-Comirnaty vaccine against B.1351-specific disease, finding somewhat reduced effectiveness of 75.0% (70.5-78.9%) against B.1.351 infection ≥ 14 days post second dose. However, effectiveness against B.1.351 severe disease ≥ 14 days post second dose was retained: 100% (73.7-100.0).3 A study from the United States of America conducted during a period when B.1.1.7 was circulating found that the Janssen – Ad26.COV 2.5 vaccine was 76.7% (95%CI: 30.3-95.3) effective against SARS-CoV-2 infection, similar to clinical trial efficacy findings conducted in a non-B.1.1.7 setting.47 While this estimate is an average estimate across all circulating viruses during the study, B.1.1.7 was the most predominant variant in the region represented by the vast majority of participants (B.1.1.7 ranged from ~25-70% of sequenced viruses reported by the US Centers for Disease Control and Prevention during the study period in this region).48 WHO recommendations Virus evolution is an expected phenomenon, and the more SARS-CoV-2 circulates, the more opportunities it has to evolve. Reducing transmission through established and proven disease control methods such as those outlined in the COVID-19 Strategic Preparedness and Response Plan, as well as avoiding introductions into animal populations are crucial aspects of the global strategy to reduce the occurrence of mutations that have negative public health implications. PHSM remain critical to curb the spread of SARS-CoV-2 and its variants. Evidence from multiple countries with extensive transmission of VOCs has indicated that the PHSM, including infection prevention and control (IPC) measures in health facilities has been effective in reducing COVID-19 case incidence, which has led to a reduction in hospitalizations and deaths among COVID-19 patients. National and local authorities are encouraged to continue strengthening existing PHSM, IPC and disease control activities. Authorities are also encouraged to strengthen surveillance and sequencing capacities and apply a systematic approach to provide a representative indication of the extent of transmission of SARSCoV-2 variants based on the local context, and to detect unusual events.
Additional resources
• Working definitions of SARS-CoV-2 Variants of Interest and Variants of Concern • COVID-19 new variants: Knowledge gaps and research • COVID-19 Situation Reports from WHO Regional Offices and partners: AFRO, AMRO/PAHO, EMRO, EURO/ECDC, SEARO, WPRO • Genomic sequencing of SARS-CoV-2: a guide to implementation for maximum impact on public health • Considerations for implementing and adjusting PHSM in the context of COVID-19
