H3N2: The Next Scare?

WITH HOSPITALS ONCE AGAIN FULL OF people sneezing and coughing into their masks, Anita (last name withheld upon request), a 39-year-old software professional and a single mom, wheedled her way into her family doctor’s consulting room earlier this month. “Both my daughters, seven and five years old, caught a bug at school that just wouldn’t let up. The girls were diagnosed with influenza and prescribed an antiviral,” says Anita. “We were assured it was nothing to worry about.” The very next day, however, her younger daughter had to be admitted to hospital for breathlessness and pneumonia-like symptoms. “It was déjà vu. About two years ago, I was in hospital for six days with SARS-CoV2. Now, watching my daughter struggling to breathe, I couldn’t believe whatever was causing her flu was a supposedly a mild virus.” The girls recovered but their throats have remained sore ever since and they are still on a mostly-liquid diet, Anita says.

The bug they had caught was H3N2, the dominant virus this flu season. Unlike SARS-CoV2, which is a coronavirus, H3N2 is a subtype of Influenza A and has been in circulation for decades as a seasonal flu. Like SARS-CoV2, it has caused an epidemic in the past—notably in 1968, when it resulted in an estimated two to four million deaths around the world. Influenza A viruses are known to be voraciously ambitious—they spread quickly and cause respiratory illnesses especially among the young and the elderly, and among those with co-morbidities. Once you are infected by a subtype of influenza, though, your immunity against it is thought to last a lifetime. Coronaviruses and influenza are both RNA viruses. To survive, these viruses undergo rapid genetic mutations, and such antigenic drifts have been responsible for heavy flu seasons across the world such as the outbreak of influenza H3N2 variant A/Fujian/411/2002 in 2003-2004.

India, now in the midst of a heavier-than-usual H3N2-dominated flu season, is understandably alert to the possibility of an outbreak especially among children. On March 4, the Indian Council of Medical Research (ICMR) confirmed that H3N2 cases have been rising since the beginning of the new year and that it has been the dominant strain in the country since December 15. “At least 92 per cent of the hospitalised SARI (severe acute respiratory infections) patients detected with the virus were showing up with fever and up to 86 per cent have cough. Additionally, 27 per cent progressed to breathlessness and 16 per cent showed wheezing symptoms. Also, 16 per cent had signs of pneumonia and 6 per cent presented with seizures,” ICMR said in a media statement. On March 14, a 58-year-old woman died in Vadodara of an H3N2 infection, taking India’s death toll due to the virus to seven. The country reported its first H3N2 death this year when an 87-year-old man from Karnataka’s Hassan district succumbed to the virus on March 1. The patient had co-morbidities including hypertension, asthma and weak kidneys, Karnataka Health Commissioner D Randeep told the media. The Central government has already issued guidelines on categorisation of patients, treatment protocols and ventilatory management to states and union territories and advised them to vaccinate health workers handling influenza cases. If the flu does not taper off as expected by the end of March, experts say India may have to look at remedial measures beyond just tracking subtypes in circulation.

There have also been deaths—at least 19, with estimates indicating over 50—and thousands of hospitalisations due to adenoviruses in West Bengal. Adenoviruses typically cause mild infections involving the upper or lower respiratory tract, gastrointestinal tract, or eyes, but this time around, with children dying of infections, the serotype in circulation needs close monitoring. ICMR labs are not required to monitor and test for adenoviruses, however, at least not yet. “ICMR has a robust multiplex assay for testing for several viruses at once. With one PCR test, we can tell if you have Respiratory Syncytial Virus (RSV), SARS CoV-2 or Influenza A or B. To identify the subtype you need to do more testing,” says Nivedita Gupta, head of virology at ICMR. Following the World Health Organization’s (WHO) recommendations for worldwide epidemiological surveillance of influenza, India has set up an integrated surveillance programme for Influenza-like Illnesses (ILI) and Severe Acute Respiratory Illnesses (SARI). The surveillance network, which includes 27 Virus Research & Diagnostic Laboratories (VRDL) around the country, besides the National Influenza Centre at the ICMR-National Institute of Virology, Pune, continues to monitor respiratory illnesses in the country even after Covid-19. Gupta, who oversees the VRDL programme, says they are currently testing 15 community samples and 10 hospital samples every week from each of the labs. The virus positivity among samples tested by ICMR labs hit a high in the ninth week of 2023, with 56 positive cases of H3N2, 16 of Influenza B and 10 of SARS-CoV2. “It is very important to keep a watch on influenza viruses with pandemic potential,” Gupta says. “Since we are a resource-poor country where flu vaccine uptake is less than 1 per cent, we have to focus on influenza rather than adenoviruses and other milder viruses that are too mild to merit full-scale monitoring. We are starting to test for RSV in children now.”

WHILE EVERY FLU season brings a different dominant subtype to the fore, there is a lot more data this year and that is how we know H3N2 is the type in circulation, Gupta points out. Others think Covid-19 may have rendered us more vulnerable to certain viruses. “H3N2 was first detected in 2010 and has been slowly spreading in various mammals and is now seen increasingly in humans. One possible reason could be that flu immunity is low now as people have protected themselves during Covid times with behaviour change, i.e., masks, distancing, hand washing, better ventilation, etc. Seasonal flu has been low during the past two years, leading to reduced population immunity,” says virologist Shahid Jameel.

“Something has changed in our immune resistance that makes us more vulnerable to one phenotype,” says Saumitra Das, a microbiologist and a professor at the Department of Microbiology and Cell Biology of the Indian Institute of Science, Bengaluru. “It is possible that because of Covid, which infected most of us, our immune systems have been dysregulated. In that case, even a known pathogen can cause serious illness.” A flu is not a Covid-19-like threat, Das adds. “Mass vaccination is not recommended for a virus our body can usually tackle easily. Vaccinating for flu is a major decision that will put a financial burden on the country and possibly cause further mutations,” he says.

Doctors say there is no need to press the panic button. “There has been an increase in the number of patients being admitted with flu-like symptoms. We are not testing for what it is, since we already know that it is most likely to be H3N2. We are yet to see the virus causing serious issues, although throat pain and cough seem to last longer than usual,” says Dr Jagadish Hiremath, founder, AASRA Hospitals, Bengaluru. There has been a parallel uptick in the number of people asking for flu shots, he says. “Every year, we offer the shot to the elderly and those with compromised immune systems such as people who have undergone a renal transplant. This year, the awareness about the flu vaccine is high and young people are walking in and asking for one.” A flu shot costs upwards of `1,600 and includes strains of influenza that are deemed to be currently in circulation. The WHO convenes in February and September each year to recommend viruses for inclusion in seasonal influenza vaccines for the northern and southern hemispheres. However, H3N2 is not part of the seasonal flu vaccine this year. The Centers for Disease Control and Prevention, US, has estimated the efficacy of this year’s flu vaccine cocktail to be only around 30 per cent against H3N2 infection, but it reduces severity, Jameel points out.

“Influenza vaccines may reduce hospitalisations, but they haven’t impacted mortality. By and large, influenza has a very low mortality rate,” says epidemiologist Jayaprakash Muliyil. “Two things keep the virus going—a new birth cohort emerging, and mutations in the virus due to which our body suddenly doesn’t recognise it. In India, you expect an outbreak every two to three years, but it is usually seasonal and does not affect most of the population.” It is when a flu virus with novel antigenic determinants, high transmissibility and antiviral resistance starts to spread that it can potentially lead to a pandemic. The 1957 H2N2 pandemic was found to have been caused by a previously circulating human H1N1 virus that had acquired three new gene segments of avian origin. Similarly, the 1968 pandemic H3N2 virus acquired two new genes from an avian virus closely related to viruses isolated from ducks in Asia in 1963. The 2009 H1N1 virus, too, contained a unique combination of gene segments from human, swine and avian Influenza A viruses. The H3N2 strain currently spreading in India may not be nearly as dangerous, but with a total of 3,038 confirmed cases of various influenza subtypes reported till March 9, it is time to mask up, once again.

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