正在监测的严重急性呼吸系统综合征冠状病毒2型变异株的风险评估：NB.1.8.1

Executive Summary NB.1.8.1has been designatedaSARS-CoV-2 variant under monitoring (VUM) with increasingproportionsglobally,whileLP.8.1isstarting to decline. Considering the available evidence, the additional public health riskposed byNB.1.8.1is evaluatedaslowat the global level.CurrentlyapprovedCOVID-19 vaccines are expectedto remaineffectiveto this variant against symptomatic and severe disease.Despite aconcurrent increaseincasesand hospitalizationsinsome countrieswhere NB.1.8.1 is widespread,current data donot indicate thatthis variant leads to more severe illness than other variants in circulation. Initial Risk Evaluation ofNB.1.8.1,23May2025NB.1.8.1is a SARS-CoV-2 variant derived fromthe recombinant variantXDV.1.5.1, with the earliest sample collected on22January2025.NB.1.8.1is one of sixVUMs tracked by the WHO and was designated as aVUM on23May2025[1,2]. Incomparison to the currently dominant SARS-CoV-2 variant,LP.8.1,NB.1.8.1has the following additional Spike mutations:T22N, F59S, G184S, A435S, V445H, and T478I.When comparedto JN.1, NB.1.8.1 has the following mutations:T22N, F59S, G184S, A435S,L455S; F456L, T478I,andQ493E.Spike mutations at position 445havebeen shown to enhance binding affinity to hACE2,which couldincreasethe variant’s transmissibility, mutations at position 435shownto reducethe neutralisation potency of class 1and class 1/4 antibodies[3], and mutations at position 478shown toenhance the evasion of Class 1/2antibodies[4].Using pseudovirusesandplasma from BA.5 breakthrough infectionswith JN.1 or XDV+F456Linfection,NB.1.8.1showed 1.5–1.6-fold reduction in neutralizationcompared to LP.8.1.1[4].In micepreviouslyimmunized with SARS-CoV-2 variants, further immunisation using monovalentKP.2 or monovalent LP.8.1mRNA vaccineselicited similar or modestly lower neutralising antibody titres against NB.1.8.1 than thoseelicited by immunising KP.2 or LP.8.1 antigens[5,6]. As of18 May 2025, there were 518 NB.1.8.1 sequences submitted to GISAID[7]from 22 countries,representing10.7% of the globally available sequences in epidemiological week17of 2025 (21to27April2025).While still low numbers, this is a significant rise in prevalence from 2.5% four weeks prior inepidemiological week14of 2025(31 Marchto6April2025), Table 1.Betweenepidemiological weeks 14 and17 of 2025,NB.1.8.1increasedinprevalence in all the three WHO regionsthat areconsistentlysharing SARS-CoV-2 sequences,i.e. an increase from8.9% to11.7% for the Western Pacific region (WPR), from1.6% to4.9% for theRegionofthe Americas (AMR), and from1.0% to6.0% for the EuropeanRegion(EUR). Thereareonly5NB.1.8.1sequences from the South East AsiaRegion(SEAR),and none fromthefrom the AfricanRegion (AFR)and theEast Mediterranean Region(EMR). WHO and its Technical Advisory Group onVirusEvolution (TAG-VE) continue to recommend that MemberStates prioritize specific actions to better address uncertainties relating to antibody escape and severity ofNB.1.8.1: •Conduct neutralization assays using human sera, representative of the affected community(ies), andsera from naive animal models infected withNB.1.8.1live virus isolates.•Perform a comparative evaluation to detect changes in rolling or ad hoc indicators of severity. WHO and its Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC) continue toregularly assess the impact of variants on the performance of COVID-19 vaccines to inform decisions onupdates to vaccine composition. In thelatest recommendation published on15 May2025, the WHOTAG-CO-VAC advised that monovalent JN.1 or KP.2remain appropriateCOVIID-19 vaccine antigens; monovalentLP.8.1 is asuitablealternativevaccine antigen[8]. The risk evaluation below follows thepublishedWHO frameworkfor risk evaluation of SARS-CoV-2 variants[9]and is based on currently available evidence.This risk evaluationwill be revised regularly as more evidenceanddata from additional countries become available.With declining prevalence of VOIs,and VUMsincreasingly unable to meet the VOI definition, WHO,on 29 November 2024,beganconductingrisk evaluationsforVUM designations in addition to VOI designations. Considering theevolution of the global epidemiological situation in relation to COVID-19andto supportmember states in addressing thecontinuousrisk posed by COVID-19 during the transition from the responseto a public health emergency of international concern to its management within broader disease preventionand control programmes,the IHR Standing Recommendations for COVID-19 issued bythe WHO DirectorGeneral’soriginally set to expire on 30 April 2025, have been extended for an additional yearwith the samecontent, until 30 April 2026[10]. Annex: * Growth advantage Level of risk: Moderate, asNB.1.8.1is growing substantially across all WHO regions with consistent SARS-CoV-2 sequence data sharing. Confidence:Low, asNB.1.8.1 expansion has only begun recently, therearelow levels of sequencing dataand thereforevariant proportions exhibit spikes,and the varian