Concerns regarding SARS-CoV-2 JN.1 mutations should be raised

Abstract

JN.1 is a new variant of SARS-CoV-2 which is a subvariant of Omicron (BA.2.86) was first discovered in the USA in September 2023. The virus’s capacity to spread and elude the immune system may be impacted by a single alteration in the spike protein, which serves as its distinguishing feature. JN.1 has been classified as an interesting variety by the World Health Organisation. JN.1 might lead to a rise in infections, or its possible influence on public health is yet premature. Current immunisations, examinations, and therapies are still anticipated to combat JN.1.

Dear Editor,

The COVID-19 (SARS-CoV-2) pandemic claimed 7.01 million lives worldwide by 13 April 2024 (https://www.worldometers.info/coronavirus/). This pandemic was a major health and socioeconomic disaster akin to the Spanish flu of 1918 (Otolorin et al. 2022). The pandemic strained healthcare systems worldwide and posed challenges for both low-income and developed countries, leading to economic collapse, job losses, and social insecurity. Despite these challenges, collaborative efforts among health organizations, governments, medical professionals, and scientists resulted in the development of effective vaccines. The global response involved comprehensive preventative measures, including quick identification and diagnosis, mass vaccination, and the rapid expansion of intensive care units in hospitals. This multipronged strategy was essential in managing the COVID-19 issue on a worldwide scale, contributing to a high recovery rate and a decline in mortality cases since February 2022. In March 2020, the global case fatality rate rose to 39%, but by July–August 2022, it dropped to below 0.3%, reflecting a significant improvement (Horita and Fukumoto 2023). This positive trend aligns with a World Health Organization (WHO) report indicating a 16.06-fold reduction in COVID-19-related fatalities from 2021 to 2023 (WHO 2023c). As a result of these advancements, governments began lifting epidemic restrictions, people resumed their normal lives, and the WHO announced that COVID-19 is no longer global health concern that requires attention in 2023 (WHO 2023b). However, several newly developing SARS-CoV-2 mutations and variations posed significant health risks in the recent past (Dhama et al. 2023). The primary goal of this letter is to raise the consciousness of the COVID-19’s new variant called JN.1, which is the Omicron subvariant (BA.2.86).

Four categories include the unique SARS-CoV-2 variations: variants of interest (VOI), variants of high consequence (VOHC), variants of concern (VOC), and variants being monitored (VBM) (Table 1). This categorization is based on factors such as the virus's virulence, transmissibility, capacity to cause serious illness, and fluctuating viral variations (Telenti et al. 2022). Thus, these groups may also have an effect on the effectiveness and diagnostic potential of immunotherapies and immunisations (Sharun et al. 2021). Because of the introduction of new variations, spontaneous sickness, and extensive vaccination, the patterns of SARS-CoV-2 transmission have evolved during the pandemic. Even while the initial pandemic was marked by outbreaks in highly vulnerable people, SARS-CoV-2 major infections in vaccinated people as well as reinfections in previously infected individuals are now becoming more prevalent (Tan et al. 2023).

Table 1 VOC, VOI and VBM of SARS-CoV-2

The WHO designated the Omicron version of COVID-19 as VOC on 26 November 2021, after it was initially found in November 2021 in Botswana, Gauteng, and South Africa (Gao et al. 2022; Silva et al. 2023). It outperformed the delta version and soon became the main lineage worldwide. The variation originated in western Europe, was recognised in the USA on 1 December 2021, and expanded to more than 150 nations, including the USA, UK, Australia, France, Germany, Denmark, Japan, Netherlands, and India (Janssen et al. 2021; Dhama et al. 2023). It is thought to be the most transmissible, most mutated, and partially resistant to COVID-19 vaccination or immunotherapy treatments now in use. The Omicron variant has many lineages, including BA.1, BA.1.1, BA.2, BA.3, BA.4, and BA.5. The WHO identified BA.2.86 as a variation under surveillance on 17 August 2023, after its discovery in a sample on 24 July 2023 (Chen et al. 2022; Desingu and Nagarajan 2022; Lambrou 2023).

By December, a new COVID-19 variety known as JN.1 (Pirola), which is the subvariant of Omicron (BA.2.86), had spread to 12 countries; among them, the USA, UK, China, and Singapore are notable. It was first identified in August in Luxembourg. Furthermore, it was found in Karakulam and Thiruvananthapuram district of Kerala, India, on December 8, 2023 (Reuters 2023). The discovery of this new variant has piqued attention and raised concerns throughout the world, and the WHO has announced as VOI on December 19, 2023 (WHO 2023a). The spike protein's lone mutation is what causes the JN.1 variation. It has an extra L455S mutation in the spike protein, giving it more capacity for immune evasion (Kaku et al. 2024). The spike protein (L455S) mutation found in JN.1 was absent from earlier versions of concern and Omicron sub-variants. Based on preliminary studies, it appears that these variations lessen the capacity of antibodies produced by vaccinations to neutralise them, which is important for JN.1. This is concerning since a number of COVID-19 vaccinations that are currently being used are based on the spike protein of the SARS-CoV-2 ancestral Wuhan strain (Sohail et al. 2024). Over 60% of COVID-19 cases in the USA are attributed to JN.1, which is mostly due to its fast expansion and domination. Furthermore, there are some symptoms that people should be aware of as they could not be as mild as those of previous Omicron variants, even if its high transmissibility and mild symptoms are like those of earlier Omicron variants (Idris and Adesola 2024). Remember that at this point in time, there is no proof that this variation is more severe or deadly than other variants.

JN.1 continues to cause major illness and mortality; hence, the WHO has classified JN.1 as VOI. The IDSA report on 17 April 2024, JN.1 is anticipated to represent 95% of all SARS-CoV-2 variations in the USA, making it the most extensively circulating variant (IDSA 2024). So far, it has spread in the UK at an 84% weekly pace; JN.1 was associated with 3600 cases worldwide. Travel restrictions were implemented by Singapore and Indonesia in December 2023, since JN.1 was responsible for over 60% of cases in Singapore (The Star 2023). Health experts have cautioned the public to exercise caution considering the increase of COVID-19 cases in Malaysia caused by the JN.1 variation (The Star 2023).

Vaccination has traditionally been recognized as the major method of protecting against viral diseases. Vaccine hesitancy is considered an imminent risk to public health by the WHO (Miyachi et al. 2020). While different factors impacting vaccine acceptance or refusal have been thoroughly stated in previous investigations (Fisher et al. 2020), the same worries persist with COVID-19 vaccines, limiting their effectiveness (Lazarus et al. 2023). The causes for vaccination non-acceptance are many and nuanced, differing not just between countries but also within parts of the same state, and they can change over time. COVID-19 vaccine adoption challenges include distribution, price, accessibility, and acceptability at the national and individual levels (Yarlagadda et al. 2022). Low vaccination rates continue to be a concern in low-income countries, with just 17.4% of persons receiving a first dose (Mathieu et al. 2020). Recent study on vaccination acceptability found that nearly one in every eight vaccinated respondents is apprehensive about booster doses. According to Lazarus et al. (2023), over two-fifths of respondents claimed they were paying less attention to new COVID-19 content. Furthermore, according to the John Hopkins University Coronavirus Resource Centre (latest updated data on 3 October 2023), less than half of the population in 65 nations received only one dose of COVID-19 vaccination (https://coronavirus.jhu.edu/vaccines/international). From Fig. 1, we can easily observe a clear declining trend of COVID-19 vaccination over the world which is reflection of the above scenario.

Fig. 1

Data visualisation for COVID-19 vaccine doses administered per 100 people (Mathieu et al. 2020)

The reference to viruses like the COVID-19-causing SARS-CoV-2 virus, immune pressure can influence the genetic diversity of the virus. Interestingly, heavy immunological pressure forced the rapid development of BA.2.86 variant to JN.1, giving it enhanced immune evasion capabilities which evade convalescent plasma substantially (Yang et al. 2024). This is consistent with the virus’s tendency to change in order to evade the host's humoral immune reaction (Forni et al. 2021). Under high immunological pressure, the virus can exploit mutations to evade the action of antibodies (Andreano et al. 2021). This event lends support to the idea that immunological pressure drives viral evolution (Yang et al. 2024).

In summary, despite the WHO’s assurance that the JN.1 variant should not be a major concern, monitoring individuals affected by JN.1 and assessing their vaccination profiles can provide valuable insights into the efficacy of existing vaccinations against newly developing variations. Investigating immune pressure in the context of vaccine development and disease management demands extensive research efforts, enabling researchers and healthcare professionals to anticipate pathogen changes and adapt strategies to uphold or enhance vaccine and treatment effectiveness. Moreover, the creation of vaccinations that target mutants or variations specifically may provide enhanced defence against new strains. Public health guidelines, however, continue to be followed in terms of improving primary healthcare systems and raising awareness of maintaining good personal cleanliness and the key strategy for stopping the spread of new variants.