CME INDIA Presentation by Dr. S. K. Gupta, MBBS, MD (Med), CFM (France), Senior Consultant Physician, Max Hosp., Delhi.

Globally, there has been a rapid increase in the proportion of JN.1 reported from just 3.3% to 27.1% over the last four weeks. Omicron, first identified in Nov 2021, has been the predominant strain driving most coronavirus infections. The virus has been undergoing several mutations both by way of recombination of multiple strains or intra-host evolution.

Evolution tree of JN.1

  • JN.1 is not a recombinant.
  • Original Omicron (B.1.1.529) mutated to BA.2 (B.1.1.529.2) which further evolved into BA.2.86 Pirola (B.1.1.529.2.86) and thereafter into JN.1 (BA.2.86.1.1 aka B.1.1.529.2.86.1.1).
JN.1 Covid Variant Drives Fresh Outbreak, Should We Be Worried?

Mutations:

  • BA.2.86 evolved for a year or so within a single patient and differed by 42 mutations from its ancestor BA.2, including 32 in the spike.
  • BA.2.86.1 had one new mutation in ORF1a.
  • BA.2.86.1.1 (JN.1) has three additional mutations, including one in spike (S: L455S).
  • Mutation at position 455 in the RBD Receptor Binding Domain draws the most attention. Without delving too deep into biochemistry, it’s important to note that concerns about mutations at this specific position were raised even before JN.1 emerged. Hence, after a few sequences with a non-suspicious pattern of JN.1, it started to attract significant attention.

Virological Character of JN.1

  • Japan recently conducted a study to investigate the virological characteristics of the JN.1
  • The study is currently available on the BioRxiv preprint* server.

Why JN.1 is important?

  • Risk Profile of JN.1
  • Newer variant assume significance owing to its ability for:
    • Growth Advantage: High risk owing to faster replication and higher transmissionImmune escape: Moderate risk Comparable to its parent lineage B.2.86 but immune escape varies across the world owing to the different vaccines used.
    • Severity of Symptoms: Low risk as the symptoms caused by JN.1 appear mild. Hence the possibility of increasing overload over the health care system is low.

WHO response to JN.1

  • Due to its rapidly increasing spread, WHO classified JN.1 as a separate variant of interest (VOI) from the parent lineage BA.2.86 on 19 Dec 2023. It was previously classified as VOI as part of BA.2.86 sub lineages.

When was JN.1 isolated?

  • Isolated in the earliest sample collected on 25 August 2023. First detected in Luxembourg.  In comparison with the parent lineage BA.2.86, JN.1 has the additional L455S mutation in the spike protein. This mutation gives it the fitness for rapid transmission

Which countries have reported higher JN.1 load?

JN.1 Covid Variant Drives Fresh Outbreak, Should We Be Worried?
  • As of 16 December 2023, there were 7344 JN.1 sequences submitted to GISAID from 41 countries, representing 27.1% of the globally available sequences.

The countries reporting the largest proportion of JN. 1 sequences are:

France (20.1%)
United States of America (14.2%)
Singapore (12.4%)
Canada (6.8%)
United Kingdom (5.8%)
Sweden (5.0%)

Will Lockdowns come again?

  • No. Highly unlikely as the disease caused by JN.1 is mild and unlikely to burden the healthcare system.
  • The governments are vigilant and focusing on community tracing via test, report, inform, and isolate) system to curb the spread.

The situation in India as of 19 December 2023.

  • India registered its first JN.1 case from southern Kerala state during a routine surveillance.  This variant was also detected in the sample of a traveller from Singapore to Tamil Nadu’s Tiruchirappalli, according to the ministry.
  • Another 15 cases of the JN.1 variant were detected in samples from Goa, according to reports.
  • While the Indian government has urged citizens to remain cautious, Kerala and Karnataka governments said they are undertaking containment measures.

Will there be a wave again?

  • Unlikely. Though JN.1 has a growth advantage, it is only RELATIVE. With built-up Hybrid Immunity following repeated natural exposures and multiple doses of vaccines tsunami spread of the virus is highly unlikely. Experience of pandemics having had 3 waves should also boost our confidence.
  • Three months have already passed since the discovery of the new variant with all international travel open.
  • However, the virus is likely to maintain a low level of endemicity or low upsurge epidemicity.

Mortality risk?

  • The virus has low potential to cause serious illness in immunocompetent individuals. News of the death in the media belonged to those suffering from multiple comorbidities.

Do we need to improvise our vaccines?

  • Vaccines used in India have shown robust immunity so far. Indian vaccines were successfully able to thwart challenges posed by earlier variants including recombinant lineage XBB.1.1. Legacy should continue.
  • However, the world is heterogeneously immune owing to the use of different vaccines. mRNA though proved excellent initially now behave differently owing to very highly specific epitopes used but still likely to prove effective owing to XBB cocktails.
  • So don’t Panic. Keep vigilant. Stay safe.

CME INDIA Learning Points

  • The most recent variant of SARS-CoV-2, JN.1 (BA.2.86.1.1), has recently surfaced. It belongs to the BA.2.86 or Pirola Omicron variant sub-lineage. Distinguished by its severe immune-evasiveness and rapid spread, JN.1 is notably different from XBB and previous virus iterations. This characteristic allows it to infect individuals with prior COVID-19 experiences and even those who have been vaccinated. The heightened immune fitness of JN.1 may be attributed to the acquisition of the 𝗟𝟰𝟱𝟱𝗦 mutation in the spike protein. Presently, there is no evidence indicating that JN.1 causes more severe illness or poses an increased risk to public health.
  • Epidemiology: Discovered in Europe in August 2023, the JN.1 variant was first identified in Luxembourg, followed by cases in England, Iceland, France, and the US. While the World Health Organization (WHO) is actively monitoring the variant, it has not yet been classified as a Variant of Concern (VOC). The reproductive number of JN.1 surpasses that of Pirola and HK.3 Covid variants, suggesting its potential to become a dominant global variant.
  • Symptoms of JN.1: JN.1 exhibits symptoms similar to other strains, including fever, cough, headaches, shortness of breath, congestion, sore throat, fatigue, loss of taste or smell, stomach cramps, and diarrhea. Vigilance is crucial as further information emerges and the medical community continues to investigate the variant.
  • COVID-19 Testing for JN.1: All COVID-19 diagnostic tests, including rapid antigen tests and PCR tests, are expected to effectively detect JN.1 and other variants, according to the Centers for Disease Control and Prevention (CDC).
  • The emergence of JN.1 underscores the dynamic nature of the COVID-19 pandemic. Proactive measures by health authorities, ongoing research, and public cooperation are essential in containing the variant’s spread and safeguarding communities. Global vigilance is imperative, recognizing that the virus’s mutational capacity requires continuous adaptation of preventive and therapeutic strategies.

CME INDIA Tail Piece

Shared by Dr. Pradeep Sahay, Giridih, Jharkhand, Bharat:

JN.1 Covid Variant Drives Fresh Outbreak, Should We Be Worried?

References:

  1. https://www.who.int/docs/default-source/coronaviruse/18122023_jn.1_ire_clean.pdf?sfvrsn=6103754a_3
  2. GISAID. Available from: https://gisaid.org/hcov19-variants/
  3. Planas D, Staropoli I, Michel V, Lemoine F, Donati F, Prot M et al. Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86 lineages combined increased fitness and antibody evasion. bioRxiv. November 2023. https://doi.org/10.1101/2023.11.20.567873


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