Review Article | Vol. 6, Issue 2 | Journal of Clinical Medical Research | Open Access |
Weimer LE1*




1National Center for Global Health, Istituto Superiore di Sanità, Rome, Italy
2Day Hospital, Department of Medicine, University Hospital, AOU Sassari, Sardegna, Italy
3Department of Infectious Diseases, DMI Istituto Superiore di Sanità, Rome, Italy
*Correspondence author: Liliana Elena Weimer, National Center for Global Health, Istituto Superiore di Sanità, Rome, Italy;
Email: liliana.weimer@iss.it
Citation: Weimer LE, et al. New COVID-19 Variant NB.1.8.1: Symptoms, Spread and The Latest Combination Therapies for Vulnerable and Immunocompromised Persons: A Literature Review and Clinical Experience in June 2025. Jour Clin Med Res. 2025;6(2):1-21.
Copyright© 2025 by Weimer LE, et al. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
| Received 17 July, 2025 | Accepted 30 June, 2025 | Published 07 July, 2025 |
Abstract
Despite the end of the pandemic, COVID-19 continues to pose a serious health threat. As of May 2025, the most notable COVID-19 variant is NB.1.8.1, informally known as “Nimbus.” This Omicron subvariant has been rapidly spreading across Asia, Europe and North America. It has been linked to a particularly severe sore throat, described by patients as feeling like “razor blades,” along with other flu-like symptoms such as fatigue, cough, fever, congestion and muscle aches. The World Health Organization (WHO) has designated NB.1.8.1 as a “Variant Under Monitoring” due to its increased immune evasion capabilities. Despite its rapid transmission, current data suggest that it does not lead to more severe disease compared to earlier strains. In addition to NB.1.8.1, other Omicron subvariants such as XEC and LP.8.1 continue to circulate. XEC, a recombinant variant fiint identified in Germany in June 2024, has been increasing in prevalence globally. It has been detected in several countries, including South Africa and is currently the most common SARS-CoV-2 subvariant reported. Health authorities continue to monitor these variants closely. Preventive measures such as vaccination, mask-wearing and good hygiene remain essential in reducing the spread of COVID-19. The challenges of outpatient administration and associated costs, monoclonal antibodies were a mainstay of the COVID-19 armamentarium from November 2020, when bamlanivimab first received US Food and Drug Administration Emergency Use Authorization (EUA), through November 2022. Ideal qualities of treatments include effectiveness in preventing hospitalization and death, safety and tolerability for patients, easy administration in the outpatient environment and cost-effectiveness. Monoclonal antibodies (mAbs) that neutralize SARS-CoV-2 fit the safety and efficacy profile in randomized clinical trials. This minireview of clinical experience explain the latest variant of concerns, the symptoms and the importance of early combination therapies for NB 1.8.1 to treat quickly immunocompromised and elderly persons.
Keywords: Monoclonal Antibodies; Early Treatment; NB 1.8.1
Introduction
Since its emergence in late 2019, the COVID-19 virus has continued to evolve through constant mutation, giving rise to new variants with varying levels of transmissibility and severity.
From Alpha to Omicron and its numerous sub-lineages, the virus has consistently demonstrated its ability to adapt and persist.
In 2025, the recent surge in cases is being attributed to a new sub-variant of Omicron, informally known as “Omicron XBB 2.3-like,” the lastest NB1.8.1 which is now drawing the attention of medicins, virologists and public health authorities worldwide [1,2]. Unlike earlier strains, this current sub-variant appears to cause milder symptoms in most people, especially those who are vaccinated or have had prior infections. However, its high transmissibility is of concern, particularly for high-density urban areas and immune-compromised individuals and ederly persons. Preliminary data suggests that the virus has now become better at escaping some of the body’s existing defenses, making it harder to stop with previous immunity alone [3].
Early research data from multiple labs are reassuring and show that existing antibodies work against the new variants. These data are also encouraging because of what it may mean for the effectiveness of the 2023-2024 COVID-19 vaccine [4,5].
Monoclonal antibodies targeting the anti-SARS-CoV-2 spike (S) protein are prescribed in high-income countries to prevent severe disease in at-risk patients. Although studies report efficacy as between 50-85%, global access is currently largely inequitable [6].
Multivariant omicron (B.1.1.529) and subvariant (BA.2 followed by BA.4 and BA.5) dominance has challenged the treatment landscape for mild-to-moderate disease, introducing considerable certainty on the efficacy of monoclonal antibodies and leading to changes to initial recommendations for some of them [7,8]. Contemporaneously, oral, direct-acting antivirals with a reported efficacy ranging from 30% (molnupiravir) to 89-90% (nirmatrelvir/ritonavir) have recently received conditional or emergency approval in some countries and been recommended in international guidelines such as the World Health Organization guidelines. S-217622, also known as ensitrelvir, a 3CL protease inhibitor that has been shown to significantly reduce the infectious viral load, is currently in phase 3 trials and waiting for emergency approval in Japan and should be submitted soon in China. The main purpose of this opinion paper is to highlight the possible strategies to optimize and protect current and future therapeutic options to treat the most vulnerable patients.
Ethical Statement
The project did not meet the definition of human subject research under the purview of the IRB according to federal regulations and therefore, was exempt.
Characteristics and Initial Risk Assessment of NB.1.8.1, 23 May 2025
NB.1.8.1 is a variant of SARS-CoV-2 that originates from the recombinant variant XDV.1.5.1, with the first sample documented on 22 January 2025.
The World Health Organization (WHO) monitors NB.1.8.1 as one of six Variants Under Monitoring (VUMs) since it was classified as such on 23 May 2025 [9,10]. In contrast to the leading SARS-CoV-2 variant, LP.8.1, NB.1.8.1 exhibits several additional Spike mutations, specifically: T22N, F59S, G184S, A435S, V445H and T478I. When assessed against the JN.1 variant, NB.1.8.1 presents the following mutations: T22N, F59S, G184S, A435S, F456L, T478I and Q493E. The Spike mutation at position 445 is known to improve the binding affinity to hACE2, potentially raising the variant’s transmissibility. Additionally, mutations at position 435 have been shown to diminish the neutralizing effectiveness of class 1 and class 1/4 antibodies, while alterations at position 478 are associated with improved evasion of Class 1/2 antibodies [11,12]. In studies using pseudoviruses and plasma from individuals with BA.5 breakthrough infections linked to JN.1 or XDV+F456L, NB.1.8.1 exhibited a reduction of 1.5 to 1.6 times in neutralization efficiency compared to LP.8.1.1. Mice that had previously been vaccinated with various SARS-CoV-2 variants demonstrated comparable or slightly lower neutralizing antibody levels against NB.1.8.1 after receiving further immunization with monovalent KP.2 or monovalent LP.8.1 mRNA vaccines, in comparison to the immunization with KP.2 or LP.8.1 antigens [13].
As of 18 May 2025, a total of 518 sequences of NB.1.8.1 have been reported to GISAID [14,15] across 22 countries, representing 10.7% of the global sequences available during epidemiological week 17 of 2025 (from 21 to 27 April 2025).
Although these numbers remain relatively modest, there has been a notable increase in prevalence from 2.5% four weeks earlier, during epidemiological week 14 of 2025 (31 March to 6 April 2025), as illustrated in Table 1.
Between epidemiological weeks 14 and 17 of 2025, NB.1.8.1’s prevalence rose across all three WHO regions that consistently report SARS-CoV-2 sequences, with an increase from 8.9% to 11.7% in the Western Pacific Region (WPR), from 1.6% to 4.9% in the Region of the Americas (AMR) and from 1.0% to 6.0% in the European Region (EUR).
Only five sequences of NB.1.8.1 have been identified in the South East Asia Region (SEAR), with no sequences reported from the African Region (AFR) or the East Mediterranean Region (EMR).
Lineage* | Countries§ | Sequences§ | 2025-14 | 2025-15 | 2025-16 | 2025-17 |
VOIs | ||||||
JN.1 | 143 | 339570 | 12.0 | 12.1 | 11.5 | 9.7 |
VUMs | ||||||
KP.3 | 85 | 61526 | 2.7 | 2.2 | 0.8 | 1.5 |
KP.3.1.1 | 89 | 117331 | 9.5 | 10.8 | 10.2 | 8.5 |
LB.1 | 99 | 25457 | 2.4 | 2.5 | 1.7 | 0.9 |
XEC | 73 | 52366 | 22.3 | 20.0 | 18.8 | 17.8 |
LP.8.1 | 51 | 15993 | 42.0 | 41.4 | 40.9 | 39.0 |
NB.1.8.1 | 22 | 518 | 2.5 | 4.1 | 7.1 | 10.7 |
Recombinant | 144 | 513365 | 6.6 | 6.9 | 8.9 | 11.8 |
Others | 111 | 35263 | 0.1 | 0.1 | – | 0.1 |
Table 1: Global proportions of SARS-CoV-2 Variants, epidemiological week 14 to 17 of 2025.
Figures by WHO, Data from Global Initiative on Sharing All Influenza Data (GISAID), extracted on 18 May 2025
*The variants listed include descendant lineages, except those individually specified elsewhere in the table.
The VOI and the VUMs that have shown increasing trends are highlighted in yellow, those that have remained stable are highlighted in blue, while those with decreasing trends are highlighted in green.
Emergence and Spread of NB.1.8.1
Origin and Detection: The variant NB.1.8.1 was initially recognized as a major factor contributing to the surge of COVID-19 infections in China. By the end of May 2025, the U. S. Centers for Disease Control and Prevention (CDC) validated its occurrence within the United States.
Global Spread: The World Health Organization (WHO) along with various health organizations have observed that NB.1.8.1 is currently circulating globally, with instances recorded in numerous nations. The swift spread of this variant has raised alarms regarding the possibility of heightened COVID-19 case numbers in different areas [16].
Variant Characteristics
Symptoms Now and Then: What’s Different?
Unlike earlier strains, this current sub-variant appears to cause milder symptoms in most people, especially those who are vaccinated or have had prior infections. However, its high transmissibility is of concern, particularly for high-density urban areas and immune-compromised individuals.
As summer brings another rise in COVID-19 infections, patients across Asia, Europe and North America are reporting a searing sore throat so intense it has earned a dramatic nickname: “razor blade throat”. Though not a new symptom, the phenomenon has gained fresh attention amid the spread of a fast-moving Omicron subvariant, formally known as NB.1.8.1 and colloquially as “Nimbus”.
Patients in China and elsewhere describe the pain as akin to “swallowing shattered glass,” with some saying they’ve been left unable to speak, eat or even stay hydrated.
Preliminary data suggests that the virus has now become better at escaping some of the body’s existing defenses, making it harder to stop with previous immunity alone.
One of the striking changes in 2025 is the symptom profile. While fever, cough and breathlessness were hallmark symptoms in 2020 and 2021, newer cases tend to exhibit more subtle signs as a pronounced, persistent Sore throat “as razor blade throat”, Nasal congestion, Headaches, Fatigue, Occasionally, gastrointestinal issues like diarrhea.
Severe complications like Acute Respiratory Distress Syndrome (ARDS) and cytokine storms have drastically declined, thanks to early detection, better clinical protocols and immunity buildup through vaccination and previous infections [19].
The CDC outlines the following as common COVID-19 symptoms:
The CDC advises seeking medical care if you experience any of the following symptoms:
SARS-CoV-2 Variants of Concern as of 28 May 2025
European Centre for Disease Prevention and Control.An agency of the European Union. Surveillance and Monitoring Comunicable Disease Threats Reports, 26 April-3 May 2025, week 18 [20]. Variant classification serves as an important communication tool for alerting EU/EEA countries about the emergence of SARS-CoV-2 variants with concerning properties likely to impact the epidemiological situation in the EU/EEA.
The ECDC Strategic Analysis of Variants in Europe (SAVE) Working Group is a multidisciplinary team comprising of ECDC Experts working in Respiratory Viruses, Microbiology, Bioinformatics, Mathematical Modelling, Epidemic Intelligence, Emergency Preparedness and Response and Vaccine-Preventable Diseases and Immunisation. Currently meetings are held once per month to assess the observed or predicted impact of currently circulating and newly emerging SARS-CoV-2 variants in the EU/EEA and globally.
ECDC utilises three categories of variant classification to communicate increasing levels of concern about a new or emerging SARS-CoV-2 variant: Variant Under Monitoring (VUM), Variant Of Interest (VOI) and Variant Of Concern (VOC). Classification criteria and recommended Member state actions are available here:
ECDC variant classification criteria and recommended Member State actions
New evidence is regularly assessed on variants detected through epidemic intelligence, genomic horizon scanning or other scientific sources. If a decision is made to add, remove or change the category for any variant, the tables are updated to reflect this change. The tables are regularly sent for consultation to ECDC stakeholders, such as the European Commission and WHO Regional Office for Europe’s joint virus characterisation working group.
Variant surveillance data, including the distribution of VOC and VOI variant proportions in the EU/EEA and detailed country-specific COVID-19 epidemiological updates are available as part of the European Respiratory Virus Surveillance Summary (ERVISS).
Useful Links: Slides from the most recent SAVE WG meeting are available in EpiPulse, with SARS-CoV-2 variant classification updates also published in ECDC’s Communicable Disease Threats Reports. To review a timeline of variant classification decisions, visit our change log.
Following classification of a VOC, VOI or VUM, multiple closely related sub-lineages may emerge. To facilitate reporting of variant detections by countries to TESSy, a table listing sub-lineages for monitored variants as of 6 May 2025 is available here.
Description of the Tables
The Table 1-3 include:
Category: Variant of Concern (VOC), Variant of Interest (VOI) or Variant Under Monitoring (VUM).
Each category is annotated as increased, reduced, similar, unclear or no evidence depending on the currently available evidence. Increased or reduced means that there is evidence demonstrating that the property is different enough for the variant compared to previously circulating variants that it is likely to have an impact on the epidemiological situation in the EU/EEA. Similar means that there is evidence that demonstrates that the property is not different enough for this variant compared to previously circulating variants that it is unlikely to have an impact. Unclear means that the current evidence is preliminary or contradictory enough to make the assessment uncertain. No evidence means that no evidence has yet been evaluated for this category. The evidence is further annotated with v or m to indicate whether the evidence is available for the variant itself (v) or for mutations associated with the variant (m).
Variants of Concern (VOC) at 28 May 2025
As of 3 March 2023, ECDC has de-escalated BA.2, BA.4 and BA.5 from its list of SARS-CoV-2 Variants Of Concern (VOC), as these parental lineages are no longer circulating. ECDC will continue to categorise and report on specific SARS-CoV-2 sub-lineages in circulation that are relevant to the epidemiological situation.
There are currently no SARS-CoV-2 variants meeting the VOC criteria.
Variants of Interest (VOI)
WHO label | Lineage + additional mutations | Country first detected (community) | Spike mutations of interest | Year and month first detected | Impact on transmissibility | Impact on immunity | Impact on severity | Transmission in EU/EEA |
Omicron | BA.2.86 | n/a | I332V, D339H, R403K, V445H, G446S, N450D, L452W, N481K, 483del, E484K, F486P | n/a | Baseline (6) | Baseline (6-8) | Baseline | Community |
Omicron | KP.3 | n/a | Q493E, F456L | n/a | No evidence | No evidence | No evidence | Dominant |
Table 1: Variants of Interest (VOI).
Variants Under Monitoring at 28 May 2025.
WHO label | Lineage + additional mutations | Country first detected (community) | Spike mutations of interest | Year and month first detected | Impact on transmissibility | Impact on immunity | Impact on severity | Transmission in EU/EEA |
Omicron | XEC | n/a | T22N, F59S, F456L, Q493E, V1104L | n/a | No evidence | No evidence | No evidence | Community |
Omicron | LP.8.1 | n/a | H445R, Q493E, F186L, R190S | n/a | No evidence | No evidence | No evidence | Community |
Omicron | NB.1.8.1 | n/a | G184S, A435S, K478I | n/a | No evidence | No evidence | No evidence | Community |
Table 2: Variants Under Monitoring (VUM).
De-Escalated Variants
These additional variants of SARS-CoV-2 have been de-escalated based on at least one the following criteria: (1) the variant is no longer circulating, (2) the variant has been circulating for a long time without any impact on the overall epidemiological situation, (3) scientific evidence demonstrates that the variant is not associated with any concerning properties.
WHO label | Lineage + additional mutations | Country first detected (community) | Spike mutations of interest | Year and month first detected | Impact on transmissibility | Impact on immunity | Impact on severity | Rationale for de-escalation |
Alpha | United Kingdom | N501Y, D614G, P681H | September 2020 | Increased (v) (9) | Similar | Increased (v) (10, 11) | Drastically reduced circulation in the EU/EEA following the emergence of Delta; little evidence of impact on vaccine induced immunity | |
n/a | B.1.1.7+E484K | United Kingdom | E484K, N501Y, D614G, P681H | December 2020 | Increased (v) (9) | Increased (v) (12, 13) | Increased (v) (10) | Very low levels of circulation in the EU/EEA |
Epsilon | USA | L452R, D614G | September 2020 | Unclear (14) | Increased (v) (14) | No evidence | No longer detected or detected at extremely low levels in the EU/EEA and available data indicating that vaccines and treatments are effective against such variant | |
n/a | B.1.616(c) | France | V483A, D614G, H655Y, G669S | February 2021 | Detection (c) (15) | No evidence | No evidence | Not detected since 2021-04-23 (16) |
Eta | Nigeria | E484K, D614G, Q677H | December 2020 | No evidence | Increased (m) (12, 17) | No evidence | No longer detected or detected at extremely low levels in the EU/EEA | |
Theta | The Philippines | E484K, N501Y, D614G, P681H | January 2021 | Increased (m) (9) | Increased (m) (12) | No evidence | No longer detected or detected at extremely low levels in the EU/EEA | |
Kappa | India | L452R, E484Q, D614G, P681R | December 2020 | Increased (v) (18) | Increased (v) (19-22) | No evidence | No longer detected or detected at extremely low levels in the EU/EEA | |
n/a | Unclear (b) | S477N, E484K, D614G, P681H | February 2021 | No evidence | Increased (m) (12, 23) | No evidence | No longer detected or detected at extremely low levels in the EU/EEA | |
n/a | India | L452R, E484Q, D614G, P681R | February 2021 | Increased (m) ((9)1) | Increased (m) (12, 14) | No evidence | No longer detected or detected at extremely low levels in the EU/EEA | |
n/a | Unclear2 | Q414K, N450K, ins214TDR, D614G | December 2020 | No evidence | No evidence | No evidence | No longer detected or detected at extremely low levels in the EU/EEA | |
n/a | A.23.1+E484K | United Kingdom | V367F, E484K, Q613H | December 2020 | No evidence | Increased (m) (12) | No evidence | No longer detected or detected at extremely low levels in the EU/EEA |
n/a | Unclear (b) | L452R, N501Y, A653V, H655Y | December 2020 | Increased (m) (9) | Increased (m) (14) | No evidence | No longer detected or detected at extremely low levels in the EU/EEA | |
n/a | Unclear (b) | E484K, N501T, H655Y | December 2020 | No evidence | Increased (m) (12) | No evidence | No longer detected or detected at extremely low levels in the EU/EEA | |
n/a | Unclear (b) | L452R, D614G | October 2020 | No evidence | Increased (m) (12) | No evidence | No longer detected or detected at extremely low levels in the EU/EEA | |
n/a | B.1.351+P384L | South Africa | P384L, K417N, E484K, N501Y, D614G, A701V | December 2020 | Increased (v) (24) | Increased (v) (25, 26) | Unclear (27) | No longer detected or detected at extremely low levels in the EU/EEA |
n/a | B.1.351+E516Q | Unclear (b) | K417N, E484K, N501Y, E516Q, D614G, A701V | January 2021 | Increased (v) (24) | Increased (v) (25, 26) | Unclear (27) | No longer detected or detected at extremely low levels in the EU/EEA |
n/a | B.1.1.7+L452R | United Kingdom | L452R, N501Y, D614G, P681H | January 2021 | Increased (v) (9) | Increased (m) (14) | Increased (v) (10) | No longer detected or detected at extremely low levels in the EU/EEA |
n/a | B.1.1.7+S494P | United Kingdom | S494P, N501Y, D614G, P681H | January 2021 | Increased (v) (9) | Increased (m) (28) | Increased (v) (10) | No longer detected or detected at extremely low levels in the EU/EEA |
Iota | USA | E484K, D614G, A701V | December 2020 | No evidence | Increased (m) (12) | No evidence | No longer detected or detected at extremely low levels in the EU/EEA | |
n/a | USA | L452R, D614G | October 2020 | No evidence | Increased (m) (14) | No evidence | Lineage withdrawn from Pango | |
n/a | USA | S477N, D614G | December 2020 | No evidence | No evidence | No evidence | Lineage withdrawn from Pango | |
Zeta | Brazil | E484K, D614G | January 2021 | No evidence | Increased (m) (12) | No evidence | No longer detected or detected at extremely low levels in the EU/EEA | |
n/a | Mexico | T478K, D614G | November 2020 | No evidence | Increased (m) (14) | No evidence | No longer detected or detected at extremely low levels in the EU/EEA | |
n/a | United Kingdom | N439K, E484K, D614G, P681H | March 2021 | No evidence | Increased (m) (12) | No evidence | No longer detected or detected at extremely low levels in the EU/EEA | |
n/a | Russian Federation | E484K, D614G, N679K, ins679GIAL | January 2021 | No evidence | Increased (m) (12) | No evidence | No longer detected or detected at extremely low levels in the EU/EEA | |
n/a | C.36+L452R | Egypt | L452R, D614G, Q677H | December 2020 | No evidence | Increased (m) (14) | No evidence | No longer detected or detected at extremely low levels in the EU/EEA |
n/a | P.1+P681H | Italy | D614G, E484K, H655Y, K417T, N501Y, P681H | February 2021 | No evidence | Unclear (29, 30) | No evidence | No longer detected or detected at extremely low levels in the EU/EEA |
Mu | Colombia | R346K, E484K, N501Y, D614G, P681H | January 2021 | Increased (m) (9) | Increased (m) (12) | No evidence | No longer detected or detected at extremely low levels in the EU/EEA | |
Lambda | Peru | L452Q, F490S, D614G | December 2020 | No evidence | Increased (v) (31, 32) | No evidence | No longer detected or detected at extremely low levels in the EU/EEA | |
n/a | United Kingdom | L452R, T478K, D614G, P681R, A222V, Y145H | June 2021 | Increased (v) (33) | Similar (v) (33, 34) | Similar (v) (33) | Delta sub-lineages will continue to be monitored within Delta VOC | |
n/a | Unclear (b) | E484K, D614G, P681H | January 2021 | No evidence | Increased (m) (12) | No evidence | No longer detected or detected at extremely low levels in the EU/EEA | |
n/a | B.1.617.2 + K417N | United Kingdom | L452R, T478K, D614G, P681R, K417N | June 2021 | No evidence | No evidence | No evidence | Delta sub-lineages will continue to be monitored within Delta VOC |
n/a | South Africa | D614G, E484K, H655Y, N501Y, N679K, Y449H | June 2021 | Increased (m) (9) | Increased (m) (12) | No evidence | No longer detected or detected at extremely low levels in the EU/EEA | |
n/a | B.1.617.2 + E484X (d) | India | L452R, T478K, D614G, P681R, E484X (d) | April 2021 | No evidence | No evidence | No evidence | Delta sub-lineages will continue to be monitored within Delta VOC |
n/a | B.1.617.2 + Q613H | India | L452R, T478K, D614G, P681R, Q613H | April 2021 | No evidence | No evidence | No evidence | Delta sub-lineages will continue to be monitored within Delta VOC |
n/a | B.1.617.2 + Q677H | India | L452R, T478K, D614G, P681R, Q677H | April 2021 | No evidence | No evidence | No evidence | Delta sub-lineages will continue to be monitored within Delta VOC |
Beta | South Africa | K417N, E484K, N501Y, D614G, A701V | September 2020 | Increased (v) (24) | Increased (v) (25, 26) | Increased (v) (11, 27) | No longer detected or detected at extremely low levels in the EU/EEA | |
Gamma | Brazil | K417T, E484K, N501Y, D614G, H655Y | December 2020 | Increased (v) (35) | Increased (v) (36) | Increased (v) (11) | No longer detected or detected at extremely low levels in the EU/EEA | |
n/a | The Republic of Congo | D614G, F490R, N394S, N501Y, P681H, R346S, Y449N, 137−145de | September 2021 | No evidence | No evidence | No evidence | No longer detected or detected at extremely low levels in the EU/EEA | |
n/a | United Kingdom | Omicron-like | January 2022 | No evidence | No evidence | No evidence | No longer detected. | |
n/a | France | NTD Delta-like; remaining Omicron-like | January 2022 | No evidence | No evidence | No evidence | No longer detected. | |
Delta | India | L452R, T478K, D614G, P681R | December 2020 | Increased (v) (37) | Increased (v) (38-40) | Increased (v) (39, 41) | Detected at extremely low levels in the EU/EEA | |
Omicron | South Africa and Botswana | (x) | November 2021 | Increased (v) (42, 43) | Increased (v)(44-46) | Reduced (v) (47-49) | Detected at extremely low levels in the EU/EEA | |
Omicron | South Africa | (z) | November 2021 | No evidence | No evidence | No evidence | Detected at extremely low levels in the EU/EEA | |
Omicron | n/a | L452X | n/a | No evidence | Increased (50) | No evidence | Detected at extremely low levels in the EU/EEA | |
Omicron | Germany | June 2022 | No evidence | No evidence | No evidence | No longer detected. | ||
Omicron | B.1.1.529 + R346X | n/a | R346X | n/a | No evidence | No evidence | No evidence | Instead of mutational proxies, tracking by lineages (majorly BQ.1 and BF.7) |
Omicron | B.1.1.529 + K444X, N460X | n/a | K444X, N460X | n/a | No evidence | Increased (m)(51) | No evidence | Instead of mutational proxies, tracking by lineages (majorly BQ.1) |
Omicron | B.1.1.529 + N460X, F490X | n/a | N460X, F490X | n/a | No evidence | Increased (m)(51) | No evidence | Instead of mutational proxies, tracking by lineages (majorly BA.2.75 and XBB) |
Omicron | n/a | K444R, L452M, N460K | n/a | No evidence | No evidence | No evidence | Detected at extremely low levels in the EU/EEA | |
Omicron | n/a | R346T, F486V | n/a | No evidence | No evidence | No evidence | Detected at extremely low levels in the EU/EEA | |
Omicron | South Africa | (y) | November 2021 | Increased (v)(42, 52) | Increased (v) (46) | Reduced (v)(53, 54) | Parental lineages are no longer circulating, ECDC monitoring sub-lineages in circulation | |
Omicron | South Africa | L452R, F486V, R493Q | January 2022 | No evidence | Increased(50, 55) | No evidence | Parental lineages are no longer circulating, ECDC monitoring sub-lineages in circulation | |
Omicron | South Africa | L452R, F486V, R493Q | February 2022 | No evidence | Increased(50, 55) | Unclear (56) | Parental lineages are no longer circulating, ECDC monitoring sub-lineages in circulation | |
Omicron | XBC (x) | n/a | N440K, F486P | n/a | No evidence | No evidence | No evidence | Detected (a) |
Omicron | n/a | R346T, K356T, F490S, | n/a | No evidence | No evidence | No evidence | Detected (a) | |
Omicron | n/a | F486P | n/a | No evidence | No evidence | No evidence | Detected (a) | |
Omicron | n/a | K444T, N460K | n/a | Increased (5) | Increased (2, 3, 61-63) | Unclear (64) | Detected at extremely low levels in the EU/EEA | |
Omicron | XBB (z) | n/a | N460K, F490S | n/a | Increased (1) | Increased(57-61) | Unclear(62) | Detected at extremely low levels in the EU/EEA |
Omicron | n/a | K444T, L452R | n/a | Increased (1, 63) | Increased (v) (57, 58, 60, 64) | No evidence | Detected at extremely low levels in the EU/EEA | |
Omicron | n/a | E180V, T478R, F486P | n/a | No evidence | No evidence | No evidence | Detected (a) | |
Omicron | India | W152R, F157L, I210V, G257S, D339H, G446S, N460K, Q493 (reversion) | May 2022 | Unclear (65) | Similar to Baseline (57, 58, 66) | No evidence | Detected at extremely low levels in the EU/EEA | |
Omicron | n/a | K444T, L452R, L455F | n/a | No evidence | No evidence | No evidence | Detected at extremely low levels in the EU/EEA | |
Omicron | XBB.1.5-like + L455F + F456L | n/a | L455F, F456L, N460K, S486P, F490S | n/a | No evidence | No evidence | No evidence | Detected at extremely low levels in the EU/EEA |
Omicron | BA.2.87.1 | South Africa | (q) (e) | 2023 September | No evidence | No evidence | No evidence | Not detected in EU/EEA |
Omicron | XBB.1.5-like | United States | N460K, S486P, F490S | n/a | Similar to Baseline (1, 2) | Reduced (v) (1, 3, 5) | Similar to Baseline (4) | No longer detected or detected at extremely low levels in the EU/EEA |
Omicron | BA.2.86 + R346T + F456L | n/a | R346T, F456L | No evidence | No evidence | No evidence | Decreased to low proportions in EU/EEA | |
Omicron | BA.2.86 + R346T | n/a | R346T | No evidence | No evidence | No evidence | Decreased to low proportions in EU/EEA | |
Omicron | BA.2.86 + F456L | n/a | F456L | No evidence | No evidence | No evidence | Mutation present in the majority of circulating descendants | |
x: A67V, Δ69-70, T95I, G142D, Δ143-145, N211I, Δ212, ins215EPE, G339D, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493R, G496S, Q498R, N501Y, Y505H, T547K, D614G, H655Y, N679K, P681H, N764K, D796Y, N856K, Q954H, N969K, L981F y: G142D, N211I, Δ212, V213G, G339D, S371F, S373P, S375F, T376A, D405N, R408S, K417N, N440K, S477N, T478K, E484A, Q493R, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, N969K z: A67V, Δ69-70, Δ143-145, N211I, Δ212, G339D, S371F, S373P, S375F, D405N, K417N, N440K, G446S, S477N, T478K, E484A, Q493R, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, D796Y, Q954H, N969K q: G75D,S98F,V126A,W152L,R190S,K417T,K444N,V445G,L452M,N481K,V642G,K679R,S691P,T791I,Y796H,D936G n/a: not applicable, no WHO label has been assigned to this variant at this time All sub-lineages of the listed lineages are also included in the variant, e.g., B.1.429.1 is included in B.1.427/B.1.429 as it is a sub-lineage of B.1.429. (a) No assessment of transmission is given for variants in the monitoring category, only detected/not detected. (b) The earliest detections from several different countries are close in time and there is no clearly demonstrated travel link to a specific country that explains the detections. (c) The property of concern for this variant was the fact that there are reports of difficulties associated with detecting it in upper respiratory tract samples. These difficulties were not caused by primer-template mismatch but rather by the virus not being present in sufficient quantities in the upper respiratory tract. (d) Any amino acid substitution (e) Preliminary mutations based on a limited number of genomes | ||||||||
Table 3: De-escalated variants.
Vaccines and Latest Monoclonal Antibodies and Their Efficacy Against New Variants at June 2025
CDC Recommendations: The World Health Organization states that currently approved COVID-19 vaccines are expected to remain effective against the NB.1.8.1 variant.
The CDC advises that everyone over the age of six months get the 2024-2025 COVID-19 vaccine, specifically the 2024-2025 Moderna COVID-19 Vaccine. People who have never received a COVID-19 vaccine, are age 65 and older, are immunocompromised, live at a long-term care facility, are pregnant, breastfeeding, trying to get pregnant, and/or want to avoid getting long COVID, should get the vaccine, especially.
Recent developments in monoclonal antibody therapies have focused on targeting newer variants of SARS-CoV-2. Here are some of the most promising monoclonal antibodies currently under investigation or authorized for use:
However, its efficacy has been reduced against some more recent Omicron sublineages, leading to evolving recommendations for its use.
Recent developments in monoclonal antibody therapies have focused on targeting newer variants of SARS-CoV-2. Here are some of the most promising monoclonal antibodies currently under investigation or authorized for use:
However, its efficacy has been reduced against some more recent Omicron sublineages, leading to evolving recommendations for its use.
Use in Immunocompromised and Elderly Populations
Immunocompromised and elderly patients are at a heightened risk of severe COVID-19 outcomes and many do not respond adequately to vaccines. Monoclonal antibodies provide an important therapeutic option for these groups, particularly in preventing disease progression and reducing hospitalization rates.
Challenges and Limitations
WHO Recommendations
The World Health Organization (WHO) alongside its Technical Advisory Group on Virus Evolution (TAG-VE) maintains its guidance that Member States should focus on particular actions to effectively manage uncertainties concerning antibody escape and the severity associated with NB.1.8.1:
The WHO, along with its Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC), routinely evaluates the influence of variants on the efficacy of COVID-19 vaccines to provide guidance for potential updates to vaccine formulations. In its most recent recommendation, dated 15 May 2025, the WHO TAG-CO-VAC indicated that monovalent JN.1 or KP.2 continue to be suitable antigens for COVID-19 vaccines, while monovalent LP.8.1 is also deemed a viable alternative vaccine antigen [21. The following risk evaluation adheres to the WHO’s published framework for assessing the risks related to SARS-CoV-2 variants and is grounded in the evidence currently accessible. This risk assessment will be updated regularly as additional evidence and data emerge from various countries. With the decreasing incidence of Variants of Interest (VOIs) and the growing inability of Variants Under Monitoring (VUMs) to satisfy the definitions for VOIs, the WHO commenced risk evaluations for VUM designations alongside VOI designations on 29 November 2024.
Conclusion
In light of the changing global epidemiological landscape regarding COVID-19 and to assist member states in managing the persistent threat posed by COVID-19 as they transition from addressing it as a public health emergency of international concern to its incorporation into broader disease prevention and control strategies, the Standing Recommendations for COVID-19 under the International Health Regulations issued by the Director General of the World Health Organization, which were originally set to end on 30 April 2025, have been prolonged for another year, maintaining the same guidelines, until 30 April 2026 [22]. The ongoing mutations of SARS-CoV-2 variants require continual advancement in the development of monoclonal Antibodies (mAbs) aimed at neutralizing new and evolving strains. For patients with compromised immune systems, monoclonal antibodies such as Evusheld, Bebtelovimab and newer combination treatment options provide essential preventive and therapeutic measures, particularly for those at elevated risk of experiencing severe illness. As the virus keeps mutating, persistent research, which includes the creation of new bispecific monoclonal antibodies and long-lasting therapies, will be crucial in enhancing health outcomes for these susceptible populations. Future studies focused on emerging variants and enhancements in vaccine strategies will be vital to thwarting potential future outbreaks and reducing the repercussions of SARS-CoV-2 on worldwide health.
Conflict of Interest
The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.
Financial Disclosure
This research received no external funding.
Acknowledgment
None.
Data Availability and Consent of Patient
Patient consent was obtained.
Author’s Contribution
All authors contributed equally in this paper.
References
https://www.who.int/activities/tracking-SARS-CoV-2-variants
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports
https://www.who.int/activities/trackingSARS-CoV-2-variants
https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports
Weimer LE1*




1National Center for Global Health, Istituto Superiore di Sanità, Rome, Italy
2Day Hospital, Department of Medicine, University Hospital, AOU Sassari, Sardegna, Italy
3Department of Infectious Diseases, DMI Istituto Superiore di Sanità, Rome, Italy
*Correspondence author: Liliana Elena Weimer, National Center for Global Health, Istituto Superiore di Sanità, Rome, Italy;
Email: liliana.weimer@iss.it
Weimer LE1*




1National Center for Global Health, Istituto Superiore di Sanità, Rome, Italy
2Day Hospital, Department of Medicine, University Hospital, AOU Sassari, Sardegna, Italy
3Department of Infectious Diseases, DMI Istituto Superiore di Sanità, Rome, Italy
*Correspondence author: Liliana Elena Weimer, National Center for Global Health, Istituto Superiore di Sanità, Rome, Italy;
Email: liliana.weimer@iss.it
Copyright© 2025 by Weimer LE, et al. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Citation: Weimer LE, et al. New COVID-19 Variant NB.1.8.1: Symptoms, Spread and The Latest Combination Therapies for Vulnerable and Immunocompromised Persons: A Literature Review and Clinical Experience in June 2025. Jour Clin Med Res. 2025;6(2):1-21.