Understanding COVID-19 variant JN.1

By Dr. Satish K Gupta*

Covid JN.1 variant drives fresh outbreak, should we be worried?

Globally, there has been a rapid increase in the proportion of JN.1 reported within the last four weeks from just 3.3% to 27.1%.

Omicron first identified in November 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

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 is JN.1 important?

Risks Profile of JN.1

Newer variants assume significance owing to their ability to:

1. Growth Advantage: High risk owing to faster replication and higher transmission

2. Immune escape: Moderate risk Comparable to its parent lineage B.2.86 but immune escape varies across the world owing to the different vaccines used

3. 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 sublineages.

When was JN.1 isolated?

JN.1 was 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?

As of  December 16, 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%), and
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 isolating systems to curb the spread.

The situation in India as of December 19, 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 Tiruchirapalli, 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?

It is 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 passed since the new variant’s discovery with all international travel open.

However, the virus is likely to maintain a low 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 behaves differently owing to very highly specific epitopes used but is still likely to prove effective owing to XBB cocktails.

So don’t panic, keep vigilant, and stay safe.

*Dr. Satish K Gupta is an MD in Medicines, a Visiting Senior Consultant Physician and Internist at Max Super Speciality Hospital, and a Clinical Assistant Professor at GS Medical College, Chaudhary Charan Singh University, Meerut. He is the author of Journey of COVID in India: A Doctor’s Perspective.