HMPV in China, India– COVID19 Redux, Is India Ready?

What is HMPV

Human metapneumovirus or HMPV is a negative-sense single-stranded RNA virus of the family Pneumoviridae and is closely related to the Avian metapneumovirus (AMPV) subgroup C. As of 2016, it was the second most common cause (after respiratory syncytial virus (RSV)) of acute respiratory tract illness in otherwise-healthy children under the age of 5 in a large US outpatient clinic. The peak age of hospitalization for infants with HMPV occurs between 6–12 months of age, slightly older than the peak of RSV, which is around 2–3 months. The clinical features and severity of HMPV are similar to those of RSV. HMPV is also an important cause of disease in older adults and infants. Human metapneumovirus was first discovered in 2001 in the Netherlands by Bernadette G. van den Hoogen and her colleagues.

It was first detected in the respiratory secretions of 28 young children in the Netherlands and had initially stood out from other common respiratory viruses because the testing methods van den Hoogen et al. had tried using (immunological assays using virus-specific antibodies and PCR-based methods using virus genome-specific primers) were only able to test for known respiratory viruses and, therefore, were unable to identify the novel virus. It was isolated using the RAP-PCR (RNA arbitrarily primed PCR) technique for identification of unknown viruses growing in cultured cells. Its flu-like symptoms, can affect people of all ages, although children below 5 years of age, older adults above 60 and those with weakened immune systems are at a higher risk.

HMPV Genetic Characteristics

It was not until researchers began applying molecular biology techniques that the genetic characteristics and portions of the genomic sequences of the virus could be identified; these techniques included the randomly primed PCR technique which obtained the limited sequence data needed to reveal a clear relationship between this new virus and the avian pneumovirus. It was this close relationship to AMPV that gave rise to this new virus being named human metapneumovirus to reflect both its identity as a metapneumovirus and its use of humans as a host organism. HMPV was responsible for 12% of cases of acute respiratory tract illness in otherwise-healthy children in a US outpatient clinic and 15% and 8% of cases (respectively) of community-acquired pneumonia requiring hospitalization in children under and over the age of 5 in the United States in 2010–2012.

Spread of HMPV is Worldwide

The virus is distributed worldwide and, in temperate regions, has a seasonal distribution generally following that of RSV and influenza virus during late winter and spring. Serologic studies have shown that by the age of 5, virtually all children across the world have been exposed to the virus. Despite near universal infection during early life, reinfections are common in older children and adults. Human metapneumovirus may cause mild upper respiratory tract infection (the common cold). However, premature infants, immunocompromised persons, and older adults >65 years are at risk for severe disease and hospitalization.

HMPV is estimated to have a 3-to-6-day incubation period and is often most active during the later winter and spring seasons in temperate climates, overlapping with the RSV and influenza seasons and possibly allowing for repeated infection. As of 2012, HMPV and its replication cycle were not well understood. Some of the principal steps of HMPV's replication cycle were studied with experiments based on the viral life cycles and reproductive measures of the rest of the Paramyxoviridae family.

Why are cases rising in China? Like many respiratory infections, HMPV is most active during late winter and spring - some experts say this is because the viruses survive better in the cold and they pass more easily from one person to another as people stay indoors more often. In northern China, the current HMPV spike coincides with low temperatures that are expected to last until March. In fact, many countries in the northern hemisphere, including but not limited to China, are experiencing an increased prevalence of HMPV, said Jacqueline Stephens, an epidemiologist at Flinders University in Australia. "While this is concerning, the increased prevalence is likely the normal seasonal increase seen in winter," she said. Data from health authorities in the US and UK shows that these countries, too, have been experiencing a spike in HMPV cases since October last year.

The first step of the HMPV replication cycle is attachment to the host cell, specifically the epithelial cells of the respiratory tract, using the G protein. This G protein contains a hydrophobic region that acts as an uncleaved signal peptide and a membrane anchor to facilitate its binding; however, because recombinant viruses that lack the G protein have still been able to replicate in vitro and in vivo, it seems that attachment via the G protein is not required for rest of the replication cycle.

Next in the cycle is the fusion of the viral and host membranes which is likely mediated by the F protein. Though the fusion mechanism is very similar to that of other Paramyxoviridae family members and involves conformational changes of the F protein, the mechanism for HMPV does not depend on the G protein for fusion like its family members, showing consistency with the previously mentioned idea that the G protein is not necessary for subsequent steps of the HMPV replication cycle. Moreover, the fusion function of the F protein has been proven by its ability to bind to host cells via integrin αvβ1 using an Arginine-Glycine-Aspartate (RGD) motif, which is speculated to be the trigger for membrane fusion events.

HMPV and Others

One main difference between HMPV and other Paramyxoviridae viruses' fusion mechanisms though is that HMPV's fusion events occur at acidic pH levels while other viruses' fusion events occur at neutral pH levels; however, more research needs to be conducted in this area to get a better understanding of what is different about the HMPV fusion mechanism and why. After fusion, the viral ribonucleoprotein (RNP) containing negative-sense viral RNA (vRNA) genome is released into the cytoplasm and acts as a template for mRNA and antigenomic cRNA synthesis. From here, most of our knowledge about HMPV transcription is derived from what we already know about RSV and other Paramyxoviridae viruses, including that leader and trailer sequences in the genome are partially complementary and act as promoters for transcription.

HMPV infects airway epithelial cells in the nose and lung. HMPV is thought to attach to the target cell via the glycoprotein (G) protein interactions with heparan sulfate and other glycosaminoglycans. The HMPV fusion (F) protein encodes an RGD (Arg-Gly-Asp) motif that engages RGD-binding integrins as cellular receptors, then mediates fusion of the cell membrane and viral envelope in a pH-independent fashion, likely within endosomes. HMPV then induces the response of chemokines and cytokines such as IL-6, IFN-alpha, TNF-alpha, IL-2, and macrophage inflammatory proteins, which in turn leads to peribronchiolar and perivascular infiltration and inflammation.

Detection of HMPV

Detection of HMPV has predominantly relied on reverse-transcriptase polymerase chain reaction (RT-PCR) technology to amplify directly from RNA extracted from respiratory specimens. Alternative more cost-effective approaches to the detection of HMPV by nucleic acid-based approaches have been employed and these include: -

    ·   Detection of HMPV antigens in nasopharyngeal secretions by immunofluorescent-antibody test.

   ·  The use of immunofluorescence staining with monoclonal antibodies to detect HMPV in nasopharyngeal secretions and shell vial cultures.

    ·   Immunofluorescence assays for detection of HMPV-specific antibodies.

  · The use of polyclonal antibodies and direct isolation in cultured cells.

Latest Outbreak in China & Contagion Film (2011)

As of January 2025, an outbreak of HMPV is in progress in China. The Chinese Center for Disease Control and Prevention published data showing that respiratory infections had risen significantly in the week of 16 to 22 December 2024; human metapneumovirus was linked to 6.2 percent of positive respiratory illness tests and 5.4 percent of respiratory-illness hospitalizations in China, more than COVID 19, rhinovirus or adenovirus. Kan Biao, head of the China CDC's National Institute for Communicable Disease Control and Prevention, announced that the rate of HMPV among children ages 14 and under was on the rise in China. Countries like Malaysia, Hong Kong, Kazakhstan, and India have also confirmed new cases of HMPV infection.

Who can forget the COVID 19 pandemic, an outbreak that destroyed the global economy, killed millions, and left many jobless. Many people are still suffering the aftermath of the pandemic that originated in China, but China originally refused to acknowledge the gravity of the situation, and refused to divulge details, and still has been highly uncooperative of efforts by the global medical bodies eager to find out the exact cause of the spread of the deadly virus. Do note COVID 19 is still affecting people in India and patients are being forced into isolation even after 3 years since the pandemic subsided.

Nobody still knows ‘what was the actual source’ of the spread of COVID 19/Corona Virus, who is patient ‘zero’ or how was the COVID 19 virus able to mutate so fast so wide. Remember the film ‘Contagion’ (2011), it was almost a mirror image what happened in 2020 and foretold the spread of a deadly virus, though in the film directed by Steven Soderberg, a cure was found and patient zero was identified. The film which had all top Hollywood actors like Kate Winslet, Matt Damon, Gwyneth Paltrow, Jude Law, Lawrence Fishburn, and Marion Cotillard. Though the film made double its cost at box office, but considering the number of A-list actors in the film, it can be considered a sort of ‘flop’, and is now available only on ‘Netflix’. The film actually depicted the outbreak of COVID 19 like global pandemic in 2011 with patient zero depicted as ‘Gwyneth Paltrow’ making a visit to China. What was depicted in the film actually did happen by end of decade. But in real life China has still not acted responsibly and not shared actual data with WHO and other authorities who are still investigating the case. We can only hope that the details of HMPV that China is giving is truthful about it, as it is a country notorious for hiding facts.

Mask, Sanitizer Back in India? No ‘Taali’ or ‘Thaali’ This Time

India has reported 2 new cases of HMPV on Tuesday, taking the overall tally to 7 in the country. The latest cases were reported in Nagpur. On Monday, 2 cases were reported in Bengaluru, and 1 each in Ahmedabad, Chennai and Salem. Indian Council of Medical Research or ICMR has said that HMPV is "already in circulation" globally, including in India. It has been around since last 20 years, so there is no need to worry say health expert, though taking precautions is necessary and better idea.

The Central government has advised states to step up surveillance for respiratory illnesses, including ILI and SARI, and spread awareness about the prevention of transmission of the HMPV. The states were also advised to enhance information, education and communication (IEC) and awareness among people regarding the prevention of transmission of the virus with simple measures similar to those followed during the Covid 19 pandemic such as: -

·  Washing hands often with soap and water.

·   Not touching eyes, nose, or mouth with unwashed hands.

· Avoiding close contact with people exhibiting symptoms of the disease.

·  Covering mouth and nose when coughing and sneezing.

Isolation wards having 15 beds each have been created in Gandhinagar, Ahmedabad and Rajkot civil hospitals as a precautionary measure after Gujarat registered its first case of HMPV, in the country. All these wards are currently vacant as no new cases of suspected (HMPV) infection has been detected. Former WHO chief scientist Soumya Swaminathan has said it is "meaningless" to keep a tab on the number of people getting HMPV infections in India. She also said only 3% of the people who are tested for Influenza-Like Illnesses (ILI) or Severe Acute Respiratory Illnesses (SARI) are found to be infected with HMPV, which has triggered concerns 5 years after COVID 19 first emerged. Ms Swaminathan also said HMPV infection has been in circulation in India for several years, but has come as a "bit of shock" to the people as it is not frequently talked about. Many state governments who have been alerted are saying there is still reason to panic or worry, just taking precautions is enough.

Whatever happens with HMPV is for time to tell, but just hope that India doesn’t have to endure once again the madness associated with COVID 19. Remember things like ‘Taal Bajao’, ‘Thaali Bajao’, ‘Ghanti Bajao’, ‘Mobile Phone Jalao’ to ward off Corona Virus!!! It was sheer madness and mass hysteria that had gripped the nations thanks to COVID 19. People didn’t realize such acts couldn’t and didn’t help ward off Corona Virus. Hope such madness doesn’t grip India once again if HMPV becomes an epidemic or pandemic. Just hope that India is better prepared this time to tackle HMPV including hospitals, testing, awareness, and vaccination if needed. Just hope there are no more ‘lockdowns’ for extended periods. If HMPV cases keep rising and turn fatal for many in India, it is better to go back to masks and sanitizers for one’s own safety.